526

Continuing Medical Education Article Anaesthesia for John Pullerits ~D eacr'c, Sigmund Ein MD FRCSC, J. Wi~liamson Belle MD r~cvc phaeochromocytoma

Phaeochromocytomas are functionally active cate- Type II-b (characterized by medullary carcinoma of the eholamine-seereting tumours of chromaffin tissue. These thyroid, Marf~oid appearance, mucosal adenomas and tumours are usually found in the adrenal medullae but phaeochromoeytoma). They can also be found as part of may occur anywhere where chromaffln tissue exists. von Hippel-Lindau syndrome which includes multiple Chromaffin tissue occurs in association with the celiac, phaeochromocytomas in association with haemangioblas- mesenteric, renal, adrenal, hypogastric, testicular and lomas of the retinae, cerebellum and other arcas of the paravertehral sympathetic nervous plexuses. Although central nervous system) most phaeochromocytomas are found in the adrenal Although most phaeochromocytoma8 are unilateral, medulla (in 90 per cent of cases), they can occur anywhere about nine per cent occur bilaterally. Bilateral tumours in the body where paraganglion ceils of the sympathetic also tend to be familial. Phaeochromocytomas may occur nervous system are found. Multiple and extra-adrenal at any age, but occur with the greatest frequency in the tumours are far more common in children (35 per cent) fourth and fifth decades of life. Ten per cent of these than in adults (eight per cent).t Although about 90 per tumours are found in children. In adults, the sex distribu- cent are benign and surgically curable, they are of special tion of the patient population shows a slightly higher interest because of the profound physiological effects female preponderance (55-60 per cent). In children, the produced by the release of large quantities of catechnla- sex ratio is reversed since approximately 70 per cent of mines. Phaeochromocytomas can also contain a variety of phaeochromocytomas occur in boys,t peptides including enkephalins, somatostatin, calcitonin, Phaeochromocytomas can vary markedly in size, rang- oxytocin and vasopressin and, rarely, can be a source of ing in weight from 1 to 4000 g but average about 100 g in clinically important ectopic hormone production. 2 the adult population and 30 g in the paediatric population. Although these turnouts account for elevated arterial The average size adult phaeochromocytoma is said to pressure in only 0.1 per cent of the population with contain, however, the equivalent of nne thousand am- diastolic hypertension, the diagnosis should be suspected poules of norepinephnne! t in any patient who develops hypertension at an early age, who has hypertension resistant to conventional therapy, or in anyone with a history of paroxysmal headaches, Pathophysielogy Since a phaeoctu-omocytoma is a tumour of the syrnpa- palpitations, sweating and pallor. Phaeochromocytomas can also be part of an autosomal- dominant multiglandular neoplastic syndrome known as TABLE Medicalsyndromes of which phaeochromocytomais a part Multiple Endocrine Adenomatosis (Table). This syn- Multiple endocrine adc:nomatosis Parathyroid adenoma/hyperplaaia drome can be categorized as Type ll-a (SippLe's syndrome -Type Ii a (Sippte'ssyndrome) Medullary carcinomaof thyroid comprising medullary carcinoma of the thyroid, parathy- Phacochromocytoma roid adenoma/hyperplasia and phaeochromocytoma) or Multiple endocrine adenomatosis Medullary carcinomaof thyroid -Type I] b Mucosal adenomas Maffanoid appearance From the Departments of Anaesthesia, Surgery (SE) and Phaeochromocytomu Paediatrics (JWB), the Hospital for Sick Children, University of Toronto, Toronto, Ontario. yon Hippel Lindau Syndrome Haemangioblastomaof the retina, Address corresporwlence to: Dr. John Pullerits, Department cerebellum or other parts of the C3/S of Anesthesin, The Children's Hospital, Boston, Phaeochromocytoma Massachusetts 02115.

CAN J ANAESTH 1988 / 3.5: S t pp526-34 Pullerits etal.: ANAESTHESIA FOR PHAEOCHROMOCYTOMA 527

Tyroslne Tyrosinehydroxylase

DOPA l Oopad~ad)o1ylase

Dopamlna

I DopamineB-hydroxylase

Phenylethanolamine N-melhynransferase Noreplnephrine Glucocofliooids Epinephrine

Dihydroxymandellc acid Metenephrlne Normetanephrineo'-. l-f

Vanlllylmandellc acid

FIGURE The pathways for synthesis and breakdown ol catecholarni.es. The rate-limiting step in catechola- mine synthesis is mediated by the enzyme tyrosine hydroxylase~

thetic nervous system, a brief review of the latter is The sympathetic neuron manufactures neurotransmit- appropriate. ters from either phenylalanine or tyrosine as is shown in This system comprises two neuroendocrine systems the Figure. In the neuronal cytoplasm, the rate-limiting linked together by a common group of low molecular enzyme, tyrosine hydroxylase, converts tyrosine to di- weight substances c',dled catecholamines which include hydroxyphenylalanine or dopa. This is then decarboxylat- dopamine, norepinephrine and epinephrine. Only norepi- ed to dopamine which is transported from the neuronal nephrine is released from post-ganglionic sympathetic cytoplasm to storage granules in the axon where it is either neurons, while both nor'epinephrine and epinephrine are stored unchanged or converted by another enzyme to synthesized in the chromaffin cells of the adrenal medulla norepinephrine. In the functional cell of the adrenal and parts of the brain. Sympathetic neurons are also medulla, the phaeochromocyte, norepinephrine leaves known as "adrenergic" neurons and the targets of their the axonal granules to be methylated in the cytoplasm by transmitters are called sympathetic or adrenergie recep- an adrenal-specific enzyme called phenylethauolamine- tors. The three general classes of these receptors include N-methyltransferase. This forms epinephrine which is the alpha-adrenergie, beta-adrenergic and the dopaminer- then stored in a different group of axoplasmic granules. gic receptors with subtypes for the alpha and beta This transformation to epinephrine requires no~ only this receptors having been ~dentified. specific enzyme bat also the high ambient concentration 528 CANADIAN JOURNAL OF ANAESTHESIA of adrenal glucocorticoids found only in the adrenal that would probably pass as essential hypertension in gland. Hence, only adrena]ly derived phaeochromocy- older patients. Urinary excretion shows relatively more tomas are capable of secreting epinephrine. The catechola- inactive metabolites than the smaller turnouts produce. mines epinephrine, norepinephrine and dopamine exert Only about one-third of phaeochromocytomas present their physiologic effects by reversibly imeracting with with the secretory crisis pattern that is described as their appropriate receptors on target tissue. Stimulation of "typical" for phaeochromocytomas.4 Moreover, it is well alpha-I receptors on vascular smooth muscle causes documented that the concentration of free circulating vaseconstriction resulting in an increase in systemic catecholamines and associated haemodynamic conditions vascular resistance and elevation of blood pressure. often have no correlation whatsoever, s Normal blood Alpha-2 stimulation by high concentrations of catechola- pressures and heart rates have been observed when the mines inhibits insulin secretion of the pancreatic islet simultaneously determined plasma catecholamine levels cells. Stimulation of cardiac beta-I receptors causes the were many times higher than normal. The reason for this rate, contractility and automaticity of the heart to discordance is not fully understood but it has been increase. postulated that a chronic increase in circulating norepi- The termination of action of a catecholamine is mostly nephfi ne levels may cau~ a corresponding decrease in the by its active reuptake by the sympathetic nerve endings. concentration of alpha-2 receptors on resistance vessels In addition, two important enzyme systems, monoamine leading to diminished presser effects) nxidase (MAn) and catechoI-O-methyltrans ferase (COMT), Phaeochromocytomas occurring within the adrenal metabolically transform the cateeholarnine~ to inactive gland generally secrete both epinephrine and norepineph- metabolites which are excreted by the kidney. Released fine but norepinephrine is the predominant catecholamine norepinephrine that has interacted with its receptors can liberated. Extra-adrenal tumours, as a rule, secrete only be taken up again by adrenergic neurons to be stored in norepincphrine. In those rare cases where epinephrine is vesicles for reuse: any norepinephrine not retaken up can the main catecholamine produced, the patient may present enter the systemic circulation where it is metabolized by with hypotension. Only one case has been reported in the enzymes MAn and COMT to vanillylmandelic acid which dopamine was the major amine secreted. (VMA), the final common product of enzymatic break- Laboratory measurement of urinary catecholamines down. Approximately five per cent of released norepine- and their metabolites, normetanephrine, metanephrine phrine eventually appears unchanged in the urine while and VMA, is helpful in the diagnosis of this condition 95 per cent is converted to metabolic byproducts. Mea- but these laboratory tests require rigid dietary and drug surements of the urinary excretion of the rnetabolites of restriction on the part of the patient and can consequently epinephrine and norepinephrine (metanephfine, normeta- produce erroneous results. nephfine and VMA) reflect the amount of catecholamine Oral clonidine has been found to suppress plasma that has been released by adrenergic and phaeochromo- catecholamine secretion in patients with essential hyper- cytoma tissue and enzymatically degraded. tension but not in patients with phaeoehromocytomas. Thus this clonidine suppression test has been useful in Diagnosis distinguishing essential hypertension patients with ele- Phaeochromocytomas have been called the "great mim- vated plasma norepinephrine levels from those patients ics" because they are nomriously variable in their secreto- with hypertension due to phaeochromocytoma. ry activity. Their clinical manifestations may range from Computerized axial totnography with or without 1131- nil to symptoms like "nervousness" or anxiety attacks and labelled meta-iodobenzyl-guanidine (MIGB) is on the signs such as episodic sweating, tremors, palpitations, other hand extremely accurate in diagnosing phaeochromo- sustained hypertension or congestive heart failure. cytomas and should be regarded as the initial localizing Generally, small tumours (<30 g) are less likely to procedure of choice.6 Indeed, since the introduction of the store and metabolize eatecholamines and more likely to CT scanner in our institution, arteriography as a localiza- release these active products into the circulation. As such tion technique has become exceedingly rare. If arteriogra- they are generally more active clinically and also more phy for tumour localization is contemplated, however, readily diagnosed. They are also more frequently associ- one should be aware that radiocontrast dyes can stimulate ated with other endocfinopathies and other endocrine catecholamine release. Thus, this radiographic technique tumours. ~ Small tumours are more likely to produce the requires the presence of an anaesthetist to manage any classical intermittent hypertensive attacks with normoten- hypertensive crises that may occur. sion between crises. The importance of diagnosing a phaeochromocytoma Large tumours (often weighing more than 250 g), on before anaesthesia and surgery cannot be overempha- the other hand, usually produce sustained hypertension sized. When an unanticipated phaeochromocytoma mani- Pullerits etal.: ANAESTHESIA FOR PHAEOCHROMOCYTOMA 529

rests itself during even the most simple operation, volume expansion and satisfactory alpha-blockade is operative mortality is still about 50 per cent. 7 In contrast, implied if an absolute drop in the haematocrit of about five mortality today during removal of a known phaeochromo- per cent is achieved. cytoma in a well-prepared patient is of the order of 0 to 3 Hypercalcaemia found preoperatively is a clue, along per cent.S with a positive family history, that the phaeochromocy- toma may be a part of a multiple endocrine adenomatosis Preoperative preparation (Type IlL A patient with co-existing hyperparathyroid- The anaesthetic preparation and management of the ism, if not causing serious hypercaleaemia, should phaeochromocytoma patient requires close communica- usually have the phaeochromocytoma excised before a tion with the intemist/paediatrician and the surgeon. parathyroidectomy is planned. Practically speaking, it is the authors' opinion that it is The surgical preparation of the patient not only in- better to involve the surgeon in the case a few days after volves assessment and treatment of cud-organ damage but the anaesthetist and internist have already agreed on and also adequate alpha-adrenergic blockade, blood volume begun drug and fluid therapy. This way the patient isn't re-expansion and the treatment of any dysrhythmias. placed on the operative list before he/she is ready. Preoperatively, the patient is started on oral phenoxybeu- The anaesthetist should be familiar with the patient's zamine; still the mainstay of pharmacologic therapy. This history and be especially careful in assessing the extent drug irreversibly alkylates alpha-1 adrenergic receptors and severity of any end-organ damage. The nature and the on vascular smooth muscle and renders them nonfunc- severity of the hypertension should be documented and tional, thereby causing vasodilation. Phenoxybenzamine any possible complications arising from it (such as at a dose of 10 mg bid PO is usually started one to two catecholamine cardiomyopathy with failure) should be weeks before surgery and is increased every one to two documented. days, not only until the hypertension is controlled, but Clinically significant cardiomyopathy has been found to until some orthostatic drop in blood pressure occurs. It occur in about 58 per cent of patients with phaeoehromo- may take 24-36 hours for phenoxybenzamine to producc eytoma and when this occurs, mortality is high. ~ The any effect: the duration of action of a single dose clinical manifestations of this cardinmyopathy are vari- approximates its 24 hour half-life. During this vascular able and non-specific nnd may inetude disturbances of volume re-expansion period, it is important not to cause cardiac rhythm or congestive heart failure with acute too precipitous a drop in the blood pressure; a high salt pulmonary oedema. ECG's should be done preoperative- intake and/or isotonic fluid administered intravenously ly on all patients since such examinations may reveal may be necessary to ensure th~s~ Aside from postural evidence of ventricular hypertrophy, dysrhythmias, is- hypolension, other side effects of phenoxybenzamine chaemia or infarction. M-mode echocard~ography is useful may include reflex tachycardia, pupillary constriction, in assessing left ventricular function in those patients nausea, sedation, weakness, gastric irritation and nasal suspected of a eardiomyopathy. stuffiness. A fasting serum glucose level should be measured in all Phentolamine, another alpha-blocking drag, has little phaeoehrolnocytoma patients to establish a baseliue. place in the preoperative management of these patients Fully 60 per cent of adult patients have hyperglycacmia aside from treating acute hypertensive crises when they preoperatively but insulin is seldom required. arise. The drug can also cause pronounced gastric upset or It is also necessary to assess renal function prior to alarming tachycardia. surgery. In addition to measuring the patient's plasma Whether it is advisable to continue pbenoxybenzamine creatinine level, a scintigraphic renal scan is useful in right up to the day of operation is still moot. In some establishing bilateral renal function and measuring the centres, phenoxybenzamine is discontinued 24 hours patient's GFR. This is especially important in the rare preoperatively to ensure that the patient is only partially event a nephrectomy may be necessary to completely alpha-blocked. During surgery on these partially blocked remove a phaeochromoeytoma. patients, surgical manipulation for the tumour can cause a A chest x-ray may reveal the presence of congestive hypertensive spike that supposedly aids the surgeon in failure, in addition to screening for the rare intrathoracic tumour localization. It is currently our feeling, however, tumour. that patients should be as completely alpha-blocked as is The circulating blood volume is usually diminished due possible. The various provocative tests for phaeochromo- to a catecholamine-induced vasoconstriction: a haemato- cytoma are potentially dangerous and unnecessary in crit greater than 45 per cent is a clue that the blood volume today's era of computerized axial tomography and we do is significantly contracted. Serial monitoring of the not believe that withholding phenoxybenzamine to allow haematocrit is a simple way of evaluating the adequacy of a patient to develop hypertensive spikes in the operating 530 CANADIAN JOURNAL OF ANAESTHESIA room is a useful tumour-localizing exercise. Practically and mineralocorticoid coverage is mandatory, but the speaking, it has also been our clinical experience that, details of the appropriate regimen are no different than for despite the most aggressive pharmacologic loading with similar surgical procedures that render a patient phenoxybenzamine, these patJ.ents will still develop some Addisonian. degree of hypertension during surgical manipulation of Premedicafion is based primarily on the preference of the tumour. the anaesthetist but in general we feel that the patient Prazosin (Minipress| a competitive alpha-I blocker should be sedated prior to arrival in the operating room to has been used preoperatively to alpha-block patients but allay anxiety which can cause release of catecholamines. has been criticized due to its failure to prevent adequately In the paediatric age group, both pentobarbital sodium perioperative hypertensive episodes, to 2 mg. kg- i per rectum or diazepam 0.3 rag- kg- i PO two The use of competitive alpha-blockers has not met with hours preop has been used with success. Morphine is much success in controlling blood pressure intraopera- undesirable on the more theoretical grounds that it can tively. It would appear that the vast amounts of catechola- release histamine, a potent inducer of catecholamine mines liberated by a surgeon squeezing a phaeochromo- release. cytoma can easily overwhelm any competitive agent that Atropine premedication, if it is to be given at all~ should reversibly occupies the alpha receptors. It requires irre- be given with caution to paediatrie phaeochromocytoma versible alkylation, not just competitive inhibition, to patients. It causes a sympathetic preponderance with ensure that alpha receptors will not respond to the high tachycardia and can cause severe hypertension. In the plasma concentrations of norepinephrine and epinephrine authors' opinion, atropine is indicated dmiug the anaes- caused by turnout manipulation. thetic induction only if a bradycardia develops that is Many patients in the literature have received beta- accompanied by significant hypotension. adrenergic blockers like propanolol or metoprolol but it is important to appreciate that beta blockers can only be Intraoperative management given after patients are well into their course of phenoxy- The times of significant intraoperalive danger to the benzamine, t Use of beta-blockers without the prior use of patient are: (1) during the anaesthetic intubation, (2) alpha-blockers can cause severe hypertension due to during tumour manipulation, and (3) immediately follow- unopposed alpha-stimulation of vascular smooth muscle. ing ligation of the tumour's venous dminagc. Extreme caution is also advised in the use of beta- The following axe essential for the safe anaesthetic blocking drugs in patients with a history of catecholamine management of the surgical resection of a pbaeochromo- cardiomyopathy. Beta-blockade in these patients may cytoma: a large bore intravenous line, an indwelling radial cause congestive failure that is refractory to therapy. artery catheter for direct pressure measurement and blood Labetalol (TrandateV), a mixed alpha- and beta- sampling, an ECG monitor, a urinary catheter, a tempera- blocking drug, has been used in phaeochromocytoma tare probe and a central venous pressure line. If the patient patients. The beta-hlockade is qualitatively silni]ar to that is suspected of having compromised left ventricular of propanolol but the alpha-block:ad.r is about 1/10~:h as function due to a catecholamine cardiomyopathy, it is potent as that of phentolamine. J~ Labetalol alone, how- better (if the patient's size allows it) to use a Swan-Ganz ever, is not able to control arterial pressure if large catheter rather than a CVP catheter. The pulmonary quantities of norepinephrine are released from the tu- wedge pressure determined by the Swan-Ganz is a more mour. i2 Indeed, since labetalol is a weaker alpha-blocker accurate reflection of left-sided filling pressures than the than a beta-blocker, it may cause an increase in blood right atrial pressure measured by the CVP line, especially pressure. in a patient with abnormal left ventricular function. It is the authors' view that generally beta-blockade of The patient should be transferred gently onto the phaeochromocytoma patients is indicated only in those operating table to avoid undue straining that may cause situations where significant cardiac dysrhythmias and/or catecholamine release. Once on the table, a precordial tachycardia are present. stethoscope, blood pressure cuff with doppler and ECG Regardless of how alpha-blockade is achieved, the leads are attached to the patient. The patient must have a benefits of preoperative alpha-blockade are dramatic. In functioning large bore intravenous line in place prior to 1951 the perioperative mortality of patients with phaeo- the induction and, if necessary, this line is started in the chromocytoma having elective resection of their tamour operating room with local infiltration of the skin with was over 50 per cent: 13 this has dropped to 0-3 per cent lidocaine. At this point sedation with 1-2 Ixg.kg-t of with the introduction of the alpha-blockirlg drugs in fentanyl is usefut in allowing cannulation of the patient's 1967. 8 radial artery with a 22- or 20-gauge catheter under local If bilateral adrenalectomy is expected, glucocortieoid anaesthesia. The ability to continuously monitor blood Pullerits etal,: ANAESTHESIA FOR PnAEOCHROMOCY'rOMA 531 pressure even prior to the actual induction is critically normally inhibit release of catecholamines. Thus the important because of the probable occurrence of marked presence of droperidol can disinhibit these chromaffin increases in blood pressure. A "sleep dose" of sodium cells and encourage catecholamine release. In light of this thiopental is then given and the patient is allowed to information, droperidol should be used intraoperativcly breathe increasing concentrations of isoflurane in nitrous with extreme caution. oxide and oxygen until clinically deep enough for As was mentioned earlier, many differenl anaesthetic intubation. Two minutes prior to the actual intubation, an techniques and drugs have been used successfully in the injection of 1.5 ~g' kg -t lidocaine is given intravenously intraoperative management of phacoehromocytoma pa- to minimize the sympathetic response to laryngoscopy. tient,~. Roizen et al. ~5 determined that phaeochromocy- The patient can then be paralyzed for the intuhation and toma patients can be managed successfully with regional the anaesthetic is maintained with NzO/O2/isoflurane anaesthesia, isoflurane, enflurane, halothane or nitrous with fentanyl either by bolus or infusion. Succinylcholine oxide with narcotics and that the choice of technique was is theoretically undesirable for tracheal intubation be- not the crucial factor determining outcome after resection cause of its stimulating effect on postganglionic sympa- of the turnout. thetic neurons and because fasciculations may cause A 0.01 per cent solution of sodium nitroprusside should raised intra-abdominal pressure sufficient to mechanical- be irmnedJately available to treat any intraoperative hyper- ly squeeze the tumour of some of its catecholamines. tension that may occur. Intermittent boluses of 1-5 mg of Isoflurane is preferred because it provides adequate phentolamine have been used successfully but nitroprus- analgesia with good muscle relaxation without sensitiza- side is our preferred agent because it acts more quickly, tion of the heart to cateeholamines. Despite its use in the lasts only one to two minutes and causes little reflex past we feel that the use of halothane can no longer be tachycardJa or tachyphylaxis. Cyanide toxicity is not a recommended lbr these cases because this vapour is problem because of the small quantities of nitroprusside dysrhythmogenic in the presence of large concentrations used. It is our experience that intravenous phemolamine of catecholamines. Continuous end-tidal CO2 and O-, works a little too slowly and lasts a little too long to be saturation monitoring is useful but results should always easily controllable in the operating room. Nitroglycerine be checked by frequent measurement of arterial blood has been used successfully but large doses are required to gases. achieve the desired effect, t8 Cardiac dysrhythrnias that Induction doses of pancuronium can cause severe occur during tumour manipulation can be treated with hypertension due to the drug's stimulant action on the lidoeaine or propanolol. Propranolol's action following sympathetic nervou s system of which the adrenal medulla its intravenous administration is approximately 30-45 is a part. t4 The use of curare for relaxation is also not minutes and may persist following the removal of the recommended because of its potential for histamine and tumour causing hypotension or myocardial depression hence catecholamine release. Atracurium and vecuron- that can result in intraoperative pulmonary oedema. 19 ium, although causing no sympathetic stimulation, are When it becomes available in Canada, a better choice than short acting and require either frequent injections or an propranolol may be esmolol. It has a rapid onset, is very infusion- For intraoperative relaxation, vecuronium short acting and thus could be titrated more precisely. seems to be the drug of choice, at least on a theoretical Within seconds of ligation of the venous drainage of a basis, since it is free of histamine t'elease. solitary phaeochromocytoma, the high concentration of However, it should be noted that metocurine, atracur- circulating norepinephrine usually falls. It is possihle that ium and curare have all been used successfully in the past if volume replacement has been inadequate up to this despite having the potential of histamine release to point the blood pressure may fall, indeed in the past some varying degrees ~s and there have been many clinical have taken the position that a fall in blood pressure at the reports documenting the safe use of pancuronium in these time of venous ligation of the tumour is proof that no other patients. tumours are present. We do not feeI that this is always The intraoperatlve use of droperido] for these patients is hue. Aggressive volume replacement can cope with a still contentious but evidence is mounting in its disfavour. dilating vascular tree at the time of venous ]igation Io the Bittar '6 has reported a series of seven cases in which the extent that no significant blood pressure fall may be injection of lnnovar| precipitated a massive hypertensive observed. Also, fully 50 per cent of phaeochromocytoma response. In one of these patients, droperidol was patients will remain hypertensive for days postoperatively reported to be the active agent. Montiel et al., 17 in an even if only one turnout was present. Plasma catechola- elegant study, has shown that intraoperative hypertension mine levels may remain above normal in some patients for may be due to droperidol's occupying the presynaptic up to 72 hours even when there is no reason to suspect dopaminergic receptors of chromaffin cells that would another tumour. 'a A precipitous drop in blood pressure is 532 CANADIAN JOURNAL OF ANAESTHESIA treated with a rapid infusion of blood or crystalloid but in tissue as possible. Reduction in the amount of the rare instance when the blood pressure cannot be raised catecholamine-secreting tissue will facilitate pharmaco- quickly enough, an infusion of a vasopressor (pbenyl- logic control of the remaining catecholamine excess. ephfine or norepinephrine) may be started as a stop.gap Chemotherapy and radiotherapy are of little benefit but measure until the newly dilated vascular space is tilted. the biochemical effects of unresectable phaeochromocy- tomas can be treated with adrenergic antagonists. A tyro- Postoperative management sine hydroxylase inhibitor, alpha-methyl-para-tyrosine, The anaesthetist would ideally like to have the patient has been used clinically, cffecting a 70-80 per cent fully awake and breathing spontaneously at the end of the t-eduction in the ulqnary excretion of catecholamines and operation. In the recovery room, the patient should be their me~abolites. 2' It can, however, cause side-effects closely monitored for blood pressure, heart rate and including postural hypotension, central nervous system rhythm, central venous pressure, urine output and level dysfunction and renal damage. Streptozotocin has had of consciousness. both failures and successes but can lead to diabetes The three important postoperative complications to mellitus. watch for are: hypertension, hypotension and hypo- The clinical course of patients with metastatic phaeo- glycaemia. chromocytonms is quite variable and the five-year survival Hypertension may be caused by pain at the operative rate averages 45 per cent. i site, hypoxia, hypercarbia, urinary retention or the presence of another as-yet-undiagnosed phaeochromocy- toma. Appropriate measures should be taken to: alleviate References pain, ensure that ventilation and oxygenation are ade- I Monger WM, GiffordRW. Pheoclu'omocytoma. New quate, drain the bladder and pharmacologically control York, Springer-Verlag, 1977. any excess catecho[amine effects should another tum0ur 2 Spark RF, ConnoUy PB, Giuckin DS etal. ACTH secre- be suspected. tion from a functioning pheochromocytnrna. N Engl 1 Significant hypotension is a rare occurrence in patients Med 1979; 2.01: 416-8. who have been alpha-blocked and adequately volume- 3 Cryer PE. Pheochromocytoma. Clinics in Endocrinology expanded preoperatively but if it develops, it is treated by and metabolism. 19851 14: I: 203-20. volume administration. An acute fall in blood pressure in 4 Flacke WE. BloorBC, FlackeJW. Adrenal medulla. In: the recovery room may indicate intra-abdominal bleeding Seminars in Anesthesia Katz RL (Ed). Orlando, FL, necessitating reoperation. Grune and 5Zratton, 1984, I11: 3: 194-206. The majority of phaeochromocytoma patients have 5 Bravo EL, Tarazi RC, Gifford RW er Circulating some degree of hyperglycaemia and glucosufia both and urinary catecholamines in pheochromocytoma. preoperatively and intraoperatively because circulat- Diagnostic and pathophysiologic implications. N Engl J ing cateeholamines act on the alpha-receptors of the Med 1979; 301: 682-6. pancreatic beta-cells to suppress insulin release. The 6 Francis tt5, Glaxer GM, Shapiro B, Sisson JC, Gross catecholamines also increase glycogenolysis and free BH. Complementary roles of CT and It3LMIBG fatty acid levels in the blood and as a consequence, scintigraphy in diagnosing pheochromocytoma. Am J provide alternate energy substrates and decrease glucose Roentgen ~.983; 141: 719-25. clearance from the blood. Within minutes of tumour 7 girkendahl WM, Leighty RD. Culp DA. Diagnosis and removal, the suppression of beta-cell function disappears treatment of patients with pheochromocytoma. Arch and plasma insulin levels rise. Postoperative hypogly- Intern Med 1965; 115: 529-36. eaemia may follow and cause loss of consciousness and 8 Roizen MF. Endocrine abnormalities and anesthesia. ASA respiratory arrest. 2~ Also, the classic symptoms of hypo- Refresher Course Lectures, 1985, pp. 253. glyeaemia may be masked in a postoperative phaeochro- 9 Van Vliet PD, Burchel fiB, Titus JL. Focal myocarditis mocytorna patient and who has been receiving analgesics associated with pheochromocytoma N Engt J Med and who may have residual beta-blockade. Consequently, 1966; 274; 1102-8. switching to a glucose-containing intravenous fluid at the 10 Nicholson JP Jr, Vaugh ED Jr, Pickering TG etai. time of tumour removal and monitoring blood glucose Pheoehromocytoma and prazosin. Ann Intern Med 1983; levels frequently for the first 24 hours postoperatively is 99: 477-9. prudent. 11 Gilman AG, Goodman LS, Gilman A. The Pharmacologic Phaeochromocytomas are malignant in about ten per Basis of Therapeutics. Sixth edition_ New York, cent of cases and some are not resectahle. Nevertheless, Macmillan, 1980, pp. 197. the surgeon should attempt to remove as much tumour 12 Ru.rsell WJ, Kaines All, Hopper MJ, Frawis~DB_ Labetalol Pullerits etal.: ANAESTHESIA FOR PHAEOCHROMOCYTOMA 533

in the preoperative managemenl of pheochromoeytoma. Anesth Intensive Care 1982; 10: I60. 13 Apgar V, Papper EM. Pheoehromocytoma - anesthetic management during surgical treatment. Arch Snrg 1951 ; 62: 634-48. 14 JonesRM, HillAB. Severe hypertension associated with paneuro~ium in a patient with a phaeochromocytoma. Can Anaesth Soc J 1981; 28: 394-6. 15 Roizen MF, Horrigan RW, Koike Met aL A prospective randomized trial of four anesthetic techniques for resec- tion ofpheoch~mocytema, Anesthesiology 1982; 57: A43. 16 Bittar DA. lnnovar-iaduccd hypertensive crises in patients with pheochromocytoma. Aneslhesiology 1979; 50: 366-9. 17 Moat~elC, Artalejo AR, Berr~te~joPM, Satlche~-Garcia P. A dopaminergic receptor in adrenal medulla as a possible site of action of droperidol-evoked hypertensive response. Anesthesiology 1986; 65: 474-9. 18 McDonaM WN, Doll WA, Schmidt N, Reynolds C, Intra- venous nitroglycerine control of blood pressure during resection of phaeochromocytoma. Can An~esth See J 1982; 29: 108-11. 19 WarkJD, Larkins RG, Pulmonary oedema after proprano- 1o1 therapy in two cases of phaeechromocytoma. Br MedJ 1978; 1: 1395-6, 20 Martin R, St. Pierre B, Moliner CR. Phaeochron'~ocytoma and post-operative hypoglyeaemia. Cart Anaesth Sor J 1979; 26: 260-2. 21 Engleman K, Horwilz D, Jequier E, Sjoerdsma A. Biochemical and pharmacologic effects of alpha methyltyrosine in man. J. Clin Invest 1968; 47: 577-94