Departments of 1 Anaesthesia and 2 Urology, Pellegrin University Hospital, 33076 Bordeaux Cedex, France. 3 Service Hypertension, Hopital Saint-André, Bordeaux Cedex, France
*Corresponding author. E-mail: patrick.tauzin-fin@chu-bordeaux.fr
Accepted for publication: November 7, 2003
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Methods. Eighteen patients with a phaeochromocytoma received a continuous i.v. infusion of urapidil 1015 mg h1 for 3 days before surgery and until the adrenal gland had been removed. Plasma catecholamine concentrations were measured before surgery, after induction of anaesthesia, at the end of pneumoperitoneal insufflation, during gland manipulation, after gland resection, and in the recovery room after extubation. Arterial pressure was recorded concomitantly. Hypertensive events were treated with boluses of nicardipine with or without esmolol.
Results. All patients had the adrenal tumour removed without any severe rise in blood pressure or other complication. Creation of a pneumoperitoneum and adrenal gland manipulation induced significant catecholamine release associated with hypertension in 6 and 12 patients, respectively. No correlation was found between hypertensive events and plasma catecholamine levels suggesting 1 receptor block with urapidil is efficacious.
Conclusions. Perioperative 1 block using i.v. urapidil is a safe and efficient alternative during surgical management of phaeochromocytoma.
Br J Anaesth 2004; 92: 51217
Keywords: adrenergic block, urapidil; complications, phaeochromocytoma; surgery, laparoscopic; sympathetic nervous system, catecholamines
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
During surgery for phaeochromocytoma, there is a risk of hypertensive events because of excessive catecholamine secretion, especially during tumour manipulation. With laparoscopic surgery, such catecholamine secretion may occur as soon as the pneumoperitoneum is created.79 It is of pivotal importance to limit the effects of such release through preoperative preparation of the patient and perioperative use of drugs that block the effects of catecholamines on 1 receptors.10 However, there is a risk of severe hypotension after the tumour removal when long acting
1 blockers are used. Urapidil, a competitive and selective short acting
1 blocker is also an agonist at central serotoninergic receptors. After an i.v. bolus dose of 2550 mg, it acts within 510 min. Its high bioavailability (72%), high clearance (1.83.8 ml min1 kg1) and short elimination half-life (24.8 h) renders urapidil, administered i.v., an alternative treatment for such patients.11 We have previously shown that perioperative infusion of urapidil may be effective in controlling intraoperative hypertension in these patients.12
The aim of this prospective study was to confirm the efficacy of perioperative i.v. urapidil by studying the relationship between plasma catecholamine levels and blood pressure during laparoscopic adrenalectomy for phaeochromocytoma.
![]() |
Patients and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Anaesthesia
The patients were premedicated with oral midazolam 5 mg. After radial artery cannulation, general anaesthesia was induced using i.v. propofol 2 mg kgl and sufentanil 0.8 µg kgl. Tracheal intubation was facilitated with cisatracurium 0.15 mg kgl. Anaesthesia was maintained with end-tidal isoflurane or sevoflurane concentrations of 1.52.5%, respectively, and a continuous infusion of sufentanil 3040 µg hl. Neuromuscular block was achieved by a continuous infusion of cisatracurium 30 mg hl. The patients were mechanically ventilated with oxygen 100%, and ventilation was adjusted to keep end-tidal PCO2 between 4.7 and 6.0 kPa. Isotonic saline or Ringers lactate solution was infused intraoperatively at a rate of 1015 ml kgl h1. The variations in systolic pressure during mechanical ventilation ( down) were used to detect hypovolaemia and to improve fluid replacement.13 Patients were then placed in the lateral position, and the pneumoperitoneum with carbon dioxide was produced with the intra-abdominal pressure maintained below 15 mm Hg.
Haemodynamic assessment
Arterial blood samples were collected for determination of plasma concentrations of epinephrine and norepinephrine before induction of anaesthesia (T0), after the inductionlaryngoscopyorotracheal intubation sequence (T1), at the end of peritoneal insufflation (T2), during adrenal gland manipulation (T3), after gland resection (T4), and in the recovery room when the trachea has been extubated and the patient was haemodynamically stable (T5). Hypertensive peaks [systolic arterial pressure (SAP) >160 mm Hg] were treated with i.v. boluses of nicardipine 24 mg to maintain SAP between 120 and 160 mm Hg. I.V. boluses of esmolol 11.5 mg kgl were used if the heart rate exceeded 100 beats minl. Hypotensive episodes (SAP <80 mm Hg) were treated with i.v. boluses of ephedrine 36 mg and a colloid infusion (Elohes® 500 ml) when down was more than 10 mm Hg.
Statistical analysis
Data are expressed as mean (SD) in the case of parametric distributions. Comparison of SAP before and after treatment was carried out using the Students paired t-test. The plasma catecholamine values were expressed as median and range because of the heterogeneity of the results. Friedmans test was used to compare their variation at the different measurement points. The relationship between plasma catecholamine levels and SAP at different surgical time points was carried out using Spearmans test for non-parametric values. The same test was used to check the influence of preoperative urinary metanephrine and nor metanephrine levels on catecholamine levels during the surgical procedure. A P-value of 0.05 was taken as the minimum level of significance.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
|
Outcome
One patient received a blood transfusion (haemoglobin <7 g dl1) because of adrenal vein injury that was controlled intraoperatively. On the first postoperative day, three patients remained hypertensive and were treated with oral urapidil 60 mg day1. The duration of hospital stay was 4 days in all cases. Six months later, all patients were normotensive and none were receiving treatment.
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Our study corroborates previous reports showing significant catecholamine release with a large variation between patients during pneumoperitoneum.7 9 The triggering factor for catecholamine release, in the absence of major surgical stimuli or visceral dissection of the phaeochromocytoma, is probably the mechanical effect of the pneumoperitoneum.14 15
Adrenal manipulation and dissection during laparoscopy also induce significant catecholamine release.9 16 There is still some controversy over whether laparoscopy produces more or less haemodynamic change, and more or less catecholamine secretion than open surgery.17 18 Resection of a phaeochromocytoma by retroperitoneoscopy can induce a hypertensive crisis.19 The triggering factor for haemodynamic instability is the adrenal gland manipulation irrespective of the type of laparoscopic procedure (trans- or retroperitoneal) performed.36 Large tumour size, prolonged duration of anaesthesia (presumably related to more difficult resection of the tumour), and increased levels of preoperative metanephrines have been considered significant independent risk factors for adverse perioperative events in open surgery.20 However, we found no correlation between preoperative urinary metanephrine and normetanephrine levels and intraoperative plasma catecholamine concentrations. Our findings suggest that intraoperative catechol amine release depends mainly on surgical manipulation of the phaeochromocytoma, and cannot be predicted by preoperative data. It has been reported that massive catecholamine release could induce malignant hypertension, adult respiratory distress syndrome,21 and reversible myocardial depression.22 In our series, two patients (nos 5 and 18) experienced unexpected high catecholamine plasma levels (321.735 pg ml1 of norepinephrine and 203.279 pg ml1 of epinephrine at T2, and 95.566 pg ml1 of norepinephrine and 161.547 pg ml1 of epinephrine at T3) without adverse effects, suggesting a protective effect of the perioperative 1 block. Further studies are needed to confirm our observations. Large tumour size (>7 cm) limits the feasibility of laparoscopic surgery, increases the duration of surgery, and increases the amount of tumour manipulation producing dramatic haemodynamic changes.20 However, in our series, we were able to remove a large tumour (patient no. 18, 10 cm) without serious haemodynamic changes.
Preoperative pharmacological preparation with l adrenergic agonists prevents peroperative hypertensive episodes.23 24 Prazosin and urapidil are the
1 agonist agents used in France even though few data are available concerning the use of urapidil for this indication. Preliminary reports have raised the possibility of using this perioperative
l block alone to control peroperative haemodynamic disorders.10 12 The use of ß adrenergic block particularly in the absence of arrhythmias is still controversial.23 24 During surgery for phaeochromocytoma, there are two problems: the risk of blood pressure surges because of catecholamine release, and the risk of cardiovascular collapse at the time of tumour removal. The haemodynamic changes are well treated by the combined use of nicardipine and esmolol. Nicardipine is a titrable short-acting calcium channel blocker without any effect on preload, and esmolol is a titrable ultra-short acting ß adrenergic blocking agent.25 26 The acute decrease in plasma catecholamines can induce cardiovascular collapse, that any persistent preoperative
1 block may potentiate.23 So a titrable short-acting
l adrenergic blocker also represents a logical treatment in such a situation.10 12 Moreover, in contrast to ß blockers and calcium channel blockers, the
l adrenergic block does not affect other aspects of blood pressure regulation. Exclusive use of nicardipine has been reported in the perioperative preparation of these patients as well as in the control of intraoperative hypertension.9 27 28 However, large doses varying from 10.5 to 31 mg h1 were necessary to control blood pressure. Intraoperative treatment of hypertension with urapidil may also be difficult in these circumstances because high doses (150300 mg) are needed, increasing the risk of sustained hypotension requiring i.v. norepinephrine therapy after removal of the tumour.29 In our series, however, the four patients with transient hypotension after tumour removal responded rapidly to treatment.
The present study shows that intraoperative hypertensive events were transient and independent of high catechol amine plasma levels, hence suggesting partial or total block of the l adrenoreceptors. The ultra-short elimination half-life of plasma catecholamines and the continuous competitive
l block produced by urapidil are probably the reason why hypertension was only transient. Doseresponse studies with urapidil would be of interest but their feasibility is limited by the low incidence of this pathology.
Induction of anaesthesia, laryngoscopy and tracheal intubation may increase sympathetic activity. This sequence was performed using a continuous infusion of urapidil without notable haemodynamic variation. The use of a ß blocker is reported to precipitate cardiac failure in these patients,23 but was necessary in six patients in our series. Interestingly, in the patient with Prinzmetals angina (patient no. 5) in whom ß blockade may increase the risk of coronary spasm,30 it was given without any side-effect because of the preoperative 1 block.
In conclusion, our findings demonstrate the surges in catecholamine release can occur during laparoscopic adrenalectomy for phaeochromocytoma. They confirm that insufflation of the pneumoperitoneum as well as tumour manipulation result in significant catecholamine release and acute haemodynamic changes. However, we found no significant correlation between the hypertensive events and plasma catecholamine levels. The perioperative use of selective 1 block with urapidil represents a simple and effective treatment of the haemodynamic variability encountered in such surgery.
![]() |
Acknowledgement |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
2 Mobius E, Nies C, Rothmund M. Surgical treatment of pheochromocytomas: laparoscopic or conventional? Surg Endos 1999; 13: 359[CrossRef][ISI]
3 Salomon L, Rabii R, Soulie M, et al. Experience with retroperitoneal laparoscopic adrenalectomy for pheochromocytoma. J Urol 2001; 165: 18714[CrossRef][ISI][Medline]
4 Horgans S, Sinanan M, Helton WS, Pelligrini CA. Use of laparoscopic techniques improves outcome from adrenalectomy. Am J Surg 1997; 173: 3714[CrossRef][ISI][Medline]
5 Winfield HN, Hamilton BD, Bravo EL, Novick AC. Laparoscopic adrenalectomy: the preferred choice? A comparison to open adrenalectomy. J Urol 1998; 160: 3259[ISI][Medline]
6 Sprung J, OHara JF, Abdelmalak B, Sarnaik A, Bravo EL. Anesthetic aspects of laparoscopic and open adrenalectomy for phaeochromocytoma. Urology 2000; 55: 33943[CrossRef][ISI][Medline]
7 Joris JL, Chiche JD, Canivet JL, Jacquet NJ, Legros JY, Lamy ML. Hemodynamic changes induced by laparoscopy and their endocrine correlates. Am J Coll Cardiol 1998; 32: 138996[CrossRef][ISI][Medline]
8 Myre K, Rostrup M, Buanes T, Stokland O. Plasma catecholamines and haemodynamic changes during pneumoperitoneum. Acta Anaesthesiol Scand 1998; 42: 3437[ISI][Medline]
9 Joris JL, Hamoir EE, Hartstein GM, et al. Hemodynamic changes and catecholamine release during laparoscopic adrenalectomy for pheochromocytoma. Anesth Analg 1999; 88: 1621
10 Valat P, Gosse P, Roche A. Urapidil au cours de la chirurgie du phéochromocytome: commencer dès la phase préopératoire. Ann Fr Anesth Réanim 1996; 15: 6989[CrossRef][ISI][Medline]
11 Dooley M, Goa KL. Urapidil. A reappraisal of its use in the management of hypertension. Drugs 1998; 56: 92955[ISI][Medline]
12 Tauzin-Fin P, Krol-Houdek MC, Gosse P, Ballanger P. Exérèse de phéochromocytomes par coeliochirurgie: effet du blockage periopératoire par lurapidil. Ann Fr Anesth Reanim 2002; 21: 46470[ISI][Medline]
13 Coriat P, Vrillon M, Perel A, et al. A comparison of systolic blood pressure variations and echocardiographic estimates of end-diastolic left ventricular size in patients after aortic surgery. Anesth Analg 1994; 78: 4653[Abstract]
14 Mann C, Millat B, Boccara G, Atger J, Colson P. Tolerance of laparoscopy for resection of phaeochromocytoma. Br J Anaesth 1996; 17: 11845
15 De la Chapelle A, Deghmani M, Dureuil B. Linsufflation péritonéale peut être un moment critique de lablation du phéochromocytome par voie laparoscopique. Ann Fr Anesth Réanim 1998; 17: 11845[CrossRef][ISI][Medline]
16 Meurisse MR, Joris JL, Hamoir EE, Hubert BM, Charlier CJ. Laparoscopic removal of pheochromocytoma. Why? When? and Who? Surg Endos 1995; 9: 4316[ISI]
17 Fernandez-Cruz L, Saenz A, Benarroch G, Sabater L, Taura P. Does hormonal function of the tumor influence the outcome of laparoscopic adrenalectomy? Surg Endos 1996; 10: 108891[CrossRef][ISI]
18 Fernandez-Cruz L, Taura P, Saenz A, Benarroch G, Sabater L. Laparoscopic approach to phéochromocytoma: hemodynamic changes and catecholamine secretion. World J Surg 1996; 20: 7628[CrossRef][ISI][Medline]
19 Atallah F, Bastide-Heulin T, Soulie M, et al. Haemodynamic changes during retroperitoneoscopic adrenalectomy for phaeochromocytoma. Br J Anaesth 2001; 86: 7313
20 Kinney MAO, Warner ME, van Heerden JA, et al. Perianesthetic risks and outcomes of pheochromocytoma and paraganglioma resection. Anesth Analg 2000; 91: 111823
21 Tauzin-Fin P, Hilbert G, Krol-Houdek MC, Gosse P, Maurette P. Mydriasis and acute pulmonary oedema complicating laparoscopic removal of phaeochromocytoma. Anaesth Intens Care 1999; 27: 6469[ISI][Medline]
22 Quezado ZN, Keiser HR, Parker MM. Reversible myocardial depression after massive catecholamine release from a pheochromocytoma. Crit Care Med 1992; 20: 54951[ISI][Medline]
23 Colson P, Ribstein J. Stratégie simplifiée pour lanesthésie du phéochromocytome. Ann Fr Anesth Réanim 1991; 10: 45662[ISI][Medline]
24 Prys-Roberts C. Phaeochromocytomarecent progress in its management. Br J Anaesth 2000; 85: 4457
25 Arai T, Hatano Y, Ishida H, Mori K. Use of nicardipine in the anesthetic management of pheochromocytoma. Anesth Analg 1986; 65: 7068[ISI][Medline]
26 Zakowski M, Haufman B, Berguson R, Tissot M, Yarmaushi L, Turndorf H. Use of esmolol during resection of pheochromocytoma: report of three cases. Anesthesiology 1989; 70: 8757[ISI][Medline]
27 Proye C, Thevenin D, Cecat P, et al. Exclusive use of calcium channel blockers in preoperative and intraoperative control of pheochromocytomas: hemodynamics and free catecholamine assays in ten consecutive patients. Surgery 1989; 106: 114954[ISI][Medline]
28 Colson P, Ryckwaert F, Ribstein J, Mann C, Dareau S. Haemodynamic heterogeneity and treatment with the calcium blocker channel nicardipine during phaeochromocytoma surgery. Acta Anaesthesiol Scand 1998; 42: 111419[ISI][Medline]
29 Steib A, Collin A, Stojeba N, Coron T, Weber JC, Beller JP. Utilisation de lurapidil au cours de la chirurgie du phéochromocytome. Ann Fr Anesth Réanim 1996; 15: 1428[CrossRef][ISI][Medline]
30 Goldbaum TS, Henochowicz S, Mustafa M, Blunda M, Lindsay J. Pheochromocytoma presenting with Prinzmetals angina. Am J Med 1986; 81: 9212[ISI][Medline]