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Anestesia y reanimación en la cirugía de las glándulas suprarrenales
Abstract
Las particularidades de la anestesia y reanimación en la cirugía de las glándulas suprarrenales se relacionan esencialmente con las alteraciones de la secreción endocrina y su brusca corrección por la exéresis (tumores secretantes); en ocasiones también pueden estar vinculadas con la amplitud de la disección quirúrgica (corticosuprarrenalomas). Los progresos realizados en el ámbito de las estrategias diagnósticas y terapéuticas han permitido reducir la mortalidad y la morbilidad perioperatorias, así como racionalizar y simplificar el tratamiento integral de los pacientes. La generalización del acceso laparoscópico en la mayoría de estos tumores es una de las modificaciones más importantes de los últimos diez años. En este capítulo se describen las principales características del tratamiento anestésico pre, intra y postoperatorio, en particular en presencia de hipercortisolismo, hiperaldosteronismo o secreción anormal de catecolaminas.
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Calcium channel blockers could be useful in the treatment of a phaeochromocytoma. In this report we describe the effects of nifedipine in a patient with a phaeochromocytoma of the urinary bladder which caused severe rises in blood pressure as a result of mechanical stimulation during voiding.
The relationship between right atrial pressure (RAP) and pulmonary artery occlusion pressure (PAOP) was found to be poor in a group of patients with pheochromocytoma, especially those with a history of congestive heart failure. The RAP and therefore central venous pressure (CVP) may be misleading in these patients, even those who are apparently free of cardiopulmonary dysfunction. Accurate assessment of left ventricular filling pressures may permit safer management of their large perioperative fluid requirements.
SNP remains an effective, reliable, and commonly used drug for the rapid reduction of significant arterial hypertension regardless of the etiology, for afterload reduction in the face of low CO when blood volume is normal or increased, and for intraoperative induced hypotension. After establishing indwelling arterial monitoring, an initial infusion rate of 0.3-0.5 micrograms.kg-1.min-1 is begun with titration as needed up to 2.0 micrograms.kg-1.min-1. Higher rates for brief periods of time (10 min) are acceptable. The use of alternative drugs to reduce the dose or shorten the duration of infusion should be considered when the 2.0 micrograms.kg-1.min-1 range is exceeded (Table 1). SNP should not be used by individuals unfamiliar with its potency and metabolic pathways, as the many reports of adverse reactions testify. Careful attention to infusion rates, particularly in patients at risk for depleted thiosulfate stores, is mandatory, and the use of other drugs in conjunction with or instead of SNP should always be considered. As with many therapeutic interventions, SNP requires careful administration to appropriately selected patients by a clinician who knows its inherent hazards. Despite its toxicity, SNP is popular because it is often the most (in some cases, the only) effective drug in some difficult clinical circumstances.
Over the last century, the central role of adrenal hormones in the maintenance of hemodynamic and metabolic homeostasis by regulation of volume and electrolytes has been defined. Controlled comparisons of perioperative management for individuals who have disorders of adrenal function are lacking. However, a review of the possible pathophysiologic changes in the adrenal cortex and techniques for their management should enable us to improve the perioperative care of patients with adrenal abnormalities.
Summary SNP remains an effective, reliable, and commonly used drug for the rapid reduction of significant arte- rial hypertension regardless of the etiology, for after- load reduction in the face of low CO when blood volume is normal or increased, and for intraoperative induced hypotension. After establishing indwelling arterial monitoring, an initial infusion rate of 0.3-0.5 pg * kg-’ . min -’ is be f: un with titration as needed up to 2.0 p.g * kg-’ * min- . Higher rates for brief periods of time (10 min) are acceptable. The use of alternative drugs to reduce the dose or shorten the duration of infusion should be considered when the 2.0 pg * kg-’ * mine1 range is exceeded (Table 1). SNP should not be used by individuals unfamiliar with its potency and metabolic pathways, as the many reports of adverse reactions testify. Careful attention to infusion rates, particularly in patients at risk for depleted thiosulfate stores, is mandatory, and the use of other drugs in conjunction with or instead of SNP should always be considered. As with many therapeu- tic interventions, SNP requires careful administration to appropriately selected patients by a clinician who knows its inherent hazards. Despite its toxicity, SNP is popular because it often the most (in some cases, the only) effective drug in some difficult clinical circumstances.
Surgical removal of phaeochromocytoma may be accompanied by acute cardiovascular changes. We report the haemodynamic changes
in seven patients with retroperitoneal laparoscopic adrenalectomy for phaeochromocytoma. Transient hypertension (systolic
pressure (SBP) >160 mm Hg) was observed in all patients during manipulation of the tumour, in two patients during pneumoretroperitoneum
insufflation, and in one patient during intubation. Small doses of nicardipine were sufficient to control these episodes of
hypertension. Transient hypotension (SBP <100 mm Hg) was observed in two patients during exsufflation and in one patient during
repositioning to the lateral position. Our observations suggest that this approach provides relative haemodynamic stability,
especially during pneumoretroperitoneum insufflation.
Br J Anaesth 2001; 86: 731–3
Objective
To investigate the efficacy of urapidil, administered either by boluses or a continuous infusion, to control hypertension during resection of phaeochromocytoma.
The only curative treatment of phaeochromocytoma consists in surgical removal. This carries a high risk due to the acute release of catecholamines. General anaesthesia cannot by itself prevent haemodynamic disturbances during surgical manipulation of the tumour. Careful preparation, based on intravascular volume repletion as well as α-, and, if required, β-adrenergic blockade, has been shown to reduce morbidity and mortality. However, this protocol is often cumbersome, and does not prevent totally the haemodynamic instability as a decrease in blood pressure at the start of treatment, or after removal of the tumour. Since voltage-dependent calcium channels are involved in both secretion and action of catecholamines, calcium-channel antagonists might be an interesting therapeutic alternative. In fact, short-term treatment by dihydropyridines may attenuate blood pressure variability during the preoperative period. During surgery, a dose-dependent reduction in systemic vascular resistances has been shown with intravenous nicardipine. However, dihydropyridines do not control cardiac adrenergic stimulation, which causes tachycardia or persistently increased blood pressure in spite of low or normal systemic vascular resistances. Such an acute cardiac hyperactivity, which can only be assessed by continuous haemodynamic monitoring, is electively sensitive to a β-adrenergic blocker rather than a calcium channel antagonist with high cardiac affinity (diltiazem, verapamil). Esmolol is available for intravenous administration. It is an ultra-short acting agent, ensuring a selective dose-related cardiac β1-blockade. Combining esmolol with nicardipine gives control over almost all episodes of haemodynamic worsening during phaeochromocytoma resection. Preoperative medical treatment no longer aims to suppress adrenergic stimulation completely, but to prevent acute haemodynamic changes. During surgery, step-by-step management of haemodynamic alterations will be based on invasive monitoring and such manoeuvers as volume loading and the use of short-acting drugs (sodium nitroprusside, nicardipine, esmolol).
Study aimThe aim of this prospective study conducted by the AFCE was to analyze the indications, approach and results of all adrenalectomies performed during the year 1997 in 17 centers, active or specialized in endocrine surgery.Patients and methodsDuring 1997, adrenalectomy was performed in 247 patients, 149 men and 98 women (mean age: 51 years). The lesion was located in the right side in 166 patients, in the left side in 99, in both sides in 28 patients and ectopic in four patients. Pheochromocytomas (n = 61 ), Conn adenomas (n = 50) and Cushing syndrome lesions (n = 48) were the most frequent in this series. Laparoscopic adrenalectomy was performed in 172 patients (70%) through a transperitoneal approach in all cases except one, and by ‘open’ surgery in 75 patients (30%).ResultsIn patients operated on by the laparoscopic approach, the mean duration of surgery was 132 min, and there were peroperative complications in 15 patients (8.7%), mainly hemorrhages. Conversion rate into laparotomy was 7%. In the postoperative course, there were three reoperations and two deaths, an early one in a patient reoperated for bleeding and a very late one in relation with necrotising acute pancreatitis. Mean duration of hospitalization was 5.8 d. Mean tumoral size was 49 mm. In patients operated on by ‘open’ surgery, the mean duration of surgery was 148 min. There was a postoperative complication in eight patients (10.6%), mostly hemorrhages, and two intraoperative deaths in relation with uncontrollable bleeding. Mean duration of hospitalization was 11 d. Mean tumoral size was 72 mm.Conclusion
Laparoscopic adrenalectomy is now indicated for the majority of adrenal tumors. Several complications observed in this series were related to the learning curve in several centers. Laparoscopic adrenalectomy is the ‘gold standard’ in uni- or bilateral benign tumors no larger than 6 or 7 cm. ‘Open’ surgery is indicated in malignant tumors, especially in adreno-cortical carcinomas, and in all large tumors.
The relationship between tumor size and the complexity of anesthetic management was studied using several values: plasma catecholamine
concentrations, requirement of vasoactive agents, surgical time, blood loss, plasma glucose concentrations, and hemodynamic
variables. Ten patients with clinical and laboratory diagnosis of pheochromocytoma were prospectively studied. Each anesthesia
was maintained using inhalational anesthetic agents. Control of arterial blood pressure (ABP), heart rate (HR), and pulmonary
artery blood pressure (PABP) was attempted with only titrating the inhalational anesthetics and adenosine triphosphate (ATP).
If the titration of both the inhalational anesthetic and ATP failed to control ABP, HR, or PABP, then phentolamine, propranolol,
trinitroglycerine, or norepinephrine was additionally used. Tumor weight was significantly correlated with amount of blood
loss, surgical time, duration of ATP requirement, maximal dose of ATP infusion used, maximal plasma glucose concentration,
and plasma total catecholamine concentration. However, the tumor weight was not correlated with hemodynamic variables. Patients
who required propranolol generally had a significantly larger tumor than those who did not. In conclusion, surgical removal
of large pheochromocytoma required more complicated anesthetic management than that of small pheochromocytoma.
Study aim: CT scan performed for non-adrenal related symptoms detects an adrenal mass or ‘incidentaloma’ in 0.4 to 4.3% of cases, and most authors advocate a non-operative policy, after minimal but careful work-up aimed at excluding pheochromocytoma and aldosteronoma. The breakthrough of laparoscopic adrenalectomy has led some to challenge this attitude. This retrospective study focused on the outcome of non-operated adrenal masses.Patients and method: From 1986 through 1999, 126 patients (64 men and 62 women) presented with an incidental mass of the adrenal fossa, and a non-surgical attitude was elicited. Mean size was 36.5 mm in diameter. All patients underwent an in-depth clinical, biochemical and imaging work-up. They have been stratified into two groups: group I: no contraindication to surgery (n = 95); and group II: contraindication to surgery (frail patients, invasive adrenal or metastatic extra-adrenal cancer) (n = 31).Results: With a mean follow-up of 4.3 years, 17 patients were lost to follow-up (13.5%), including 11/95 in group I; 36 were dead (28.5 %), including 12/95 in group I (no adrenal-related death) and 24/31 in group II; 72 were alive and well without operation, including only one in group II; one patient was operated for a benign adrenal adenoma removed at the time of surgery for aortic aneurysm.Conclusion: Careful clinical, biochemical, imaging and nor-iodo-cholesterol scintigraphy with definite uptake by the adrenal mass, a strong indicator of benignancy, allows surgical indication to be postponed, and is likely to cancel it if, at one-year follow-up, imaging studies show no change in the mass.
A total of 102 patients with phaeochromocytoma who underwent surgery by the same team between 1964 and 1976 were allocated
to three groups according to the anaesthetic protocol used: (1) balanced anaesthesia and control of hypotension with noradrenaline;
(2) anaesthesia with halothane and replacement of blood volume; (3) neuroleptanalgesia (droperidol and phenoperidine) and
replacement of blood volume. None of the patients in any of the three groups received adrenergic inhibitors before anaesthesia.
Comparison of the results in the three groups revealed that the major factor responsible for reduction of operative mortality
to almost zero was control of hypotension by replacement of blood volume rather than by the use of noradrenaline following
resection of the tumour, whereas the type of anaesthetic agent used was of secondary importance.
The paper reviews the hitherto rather scarce literature concerned with cardiac changes in phaeochromocytoma, primary hyperaldosteronism and Cushing syndrome, and presents the authors' own echocardiographic findings in these diseases. In phaeochromocytoma they found a slight thickening of the interventricular septum which, however, did not fulfil the criteria of asymmetric left ventricular hypertrophy. Also other parameters showed higher values attesting to an increased left ventricular mass, however, without exceeding normal limits. Focal disturbances of left ventricular kinetics and the decrease in LV systolic function were non significant. The picture of obstructive hypertrophic cardiomyopathy, frequently mentioned in the literature, was observed only once, giving grounds to the suspicion that it is only a nonspecific manifestation of the hypercontractile state of the myocardium. In primary hyperaldosteronism only slight posterior LV wall thickening and an increase in the LV mass index were found, compared to control group. No significant changes were found in Cushing syndrome besides a tendency to concentric LV hypertrophy. Echocardiographic changes observed in all three affections disappeared after successful surgical or drug treatment.
FrancescoGreco, M. RaschidHoda, JensRassweiler, DirkFahlenkamp, Dietmar A.Neisius, AndreasKutta, Joachim W.Thüroff, AndreasKrause, Walter L.Strohmaier, AlexanderBachmann, LotharHertle, GralfPopken, SerdarDeger, ChristianDoehn, DieterJocham, TillmannLoch, SvenLahme, VolkerJanitzky, Christian P.Gilfrich, TheodorKlotz, BerndKopper, UdoRebmann, TilmanKälbe, UlrichWetterauer, ArminLeitenberger, JörgRaßler, FelixKawan, AntoninoInferrera, SigridWagner, PaoloFornara. (2011) Laparoscopic adrenalectomy in urological centres - the experience of the German Laparoscopic Working Group. BJU International 108, 1646-1651
CrossRef
Experimental findings suggest that catecholamines increase protein synthesis and play a role in cardiac hypertrophy. We hypothesize that elevated circulating plasma catecholamines in pheochromocytoma influence cardiac structural and functional remodeling. We compared 15 patients with surgically proven pheochromocytoma and 15 with untreated essential hypertension; we matched the patients for age, sex, body surface area, and blood pressure (BP) levels. Left ventricular hypertrophy (LVH) was identified by M-mode echocardiography in six patients with pheochromocytoma and in four with essential hypertension. Among both groups there were no differences in cardiac structure, no correlation between left ventricular mass and BP, no significant differences in mitral E-F slope, no correlation between either plasma norepinephrine or plasma epinephrine levels, and no differences in the left ventricular structural indices measured. In the pheochromocytoma group, left ventricular end systolic stress and end systolic diameter were significantly lower and left ventricular percent fractional shortening was higher. Plasma norepinephrine levels were higher in the pheochromocytoma group, but did not differ among patients of that group with and without LVH. We conclude that in both pheochromocytoma and essential hypertension, only a subset of patients develop evidence of LVH, and that in pheochromocytoma, the elevation of circulating plasma catecholamines is not necessarily associated with LVH. These results indicate that factors other than catecholamines and BP determine the development of LVH in pheochromocytoma.
The incidence, symptoms, signs and differential diagnosis of phaeochromocytoma have been discussed in detail. Current methods of biochemical diagnosis and anatomical localization of the tumour have been reviewed, the appropriate pharmacotherapy and other aspects of medical management have been outlined. Also detailed herein are anaesthetic management and surgical approach, the pitfalls of drug administration in known or suspected phaeochromocytoma, and particular considerations when phaeochromocytoma is malignant or when it coexists with pregnancy. Three decades ago, the diagnosis and management of phaeochromocytoma was succinctly summarized as follows: 'think of it, confirm it, find it and remove it' (Manger and Gifford, 1977; Ross, 1962). Despite the availability of sophisticated diagnostic tests and the significant progress in management, where phaeochromocytoma is concerned, a high index of suspicion ('thinking of it') remains the physician's most valuable tool.
We had five cases of surgical removal of pheochromocytoma by continuous intravenous injection of prostaglandin E1. During anesthesia, we used Swan-Ganz catheter for circulatory monitoring and measured plasma catecholamines. When PGE1 dose was increased from 0.05 to 0.1 and 0.15 microgram.kg-1.min-1, total systemic vascular resistance and mean arterial pressure were decreased but heart rate and cardiac output were not significantly altered from the preanesthetic values. Plasma catecholamines were also similar to the preanesthetic values. Therefore, the results suggest that the mechanism of suppression of hypertension by PGE1 is by affecting vascular beds directly rather than by diminishing catecholamine excretion from sympathetic nerve and adrenal medulla. During manipulation of pheochromocytoma, mean arterial blood pressure increased extremely. Although PGE1 was injected at a rate of 0.3 to 0.5 microgram.kg-1.min-1 in some cases, we could not suppress the elevation of blood pressure. PGE1 alone could not normalize blood pressure and heart rate, and other cardiovascular agents were necessary.
During an 8-year-period from 1981 to 1989, a total of 6 of 45 patients with pheochromocytoma developed severe hypoglycemia (plasma glucose, 12–50 mg/dl) 2–4 1/2 hours after removal of the tumor. In order to elucidate the pathogenesis of the hypoglycemic attack, the levels of plasma immunoreactive insulin (IRI) and glucose were sequentially measured at surgery in 10 patients with pheochromocytoma, from the beginning of the operation until usually 5 hours after tumor resection. The same examinations were carried out in 4 patients with primary aldosteronism and 1 patient with Cushing's syndrome as controls. The highest plasma IRI levels observed in the 2 patients with postexcisional hypoglycemia were 174 and 2,081
μ
U/ml and those in the 8 patients without hypoglycemia were 13–222
μ
U/ml (mean, 77), but they were only 14–33
μ
U/ml (mean, 22) in the 5 control patients. The mean of the highest plasma IRI/glucose ratios in the immediate postoperative phase was 1.37±0.87 in the 10 patients with pheochromocytoma but only 0.16±0.04 in the 5 control patients (p<0.01). Review of the clinical data in our series disclosed that patients with higher levels of preoperative urinary epinephrine excretion and those with either diabetes mellitus or impaired glucose tolerance tended to develop postoperative hypoglycemia. These observations suggest that endogeneous insulin secretion is suppressed by increased plasma catecholamines, and that excessive rebound secretion of insulin after removal of a pheochromocytoma is a rather common phenomenon. Intravenous infusion of glucose is necessary and plasma glucose levels should be monitored after resection of a pheochromocytoma.
We examined the hemodynamic features of 24 untreated patients with surgically proven pheochromocytoma during steady-state periods and compared them with 24 untreated essential hypertensive patients individually matched for sex, age, body surface area, and arterial blood pressure. We found that, despite having 10-fold higher levels of circulating catecholamines, pheochromocytoma patients have hemodynamic characteristics similar to patients with essential hypertension and that, in individual patients, the ratio of circulating norepinephrine to epinephrine had no relation to the hemodynamic profile. In both groups, increased total peripheral resistance is primarily responsible for maintenance of hypertension. These results suggest that, unlike the acute administration of catecholamines, long-term exposure to high levels of circulating catecholamines does not produce hemodynamic responses characteristic of this group of compounds. This might be due in part to desensitization of the cardiovascular system to catecholamines and might explain the clinical observation that some patients can be completely asymptomatic despite harboring an actively catecholamine-secreting pheochromocytoma.
The postoperative management of phaeochromocytoma with special reference to glucose levels is discussed and precautions are
elucidated.
This study investigates the role of nicardipine hydrochloride in preoperative and intraoperative blood pressure control and intraoperative catecholamines (norepinephrine and epinephrine) release in 10 patients undergoing pheochromocytoma resection. Nicardipine was used orally in the preoperative period for either 1 or 8 days (60 to 120 mg/24 hr) and then was infused during anesthesia until tumor removal, continuously at a rate of 2.5 to 7.5 micrograms/kg/min, depending on systolic arterial pressure level. All patients were successfully operated on. No severe hypertensive crisis occurred during tumor manipulation, although several patients had a 3- to 85-fold (norepinephrine) and 3- to 40-fold (epinephrine) increase of catecholamines from baseline levels. Hemodynamics data suggest that nicardipine caused significant inhibition of vascular smooth muscle contraction (42% decrease in systemic vascular resistance); calcium-dependent catecholamines release was not inhibited by nicardipine infused as mentioned. Use of nicardipine may be recommended for perioperative and intraoperative control of pheochromocytomas and might substitute for routine alpha-adrenergic blockade.
Seventeen anaesthetics are described in 16 patients with phaeochromocytoma in whom magnesium sulphate (MgSO4) was the principal anti-adrenergic agent used. In 15 of the 17 anaesthetics, MgSO4 produced satisfactory control of cardiovascular changes at induction and tracheal intubation, but in four of these additional
sodium nitroprusside was required to control the arterial pressure during handling of the tumour. In one pregnant patient
undergoing Caesarean section, MgSO4 was ineffective in controlling cardiovascular disturbances because of inadequate serum magnesium concentrations. This patient
had a magnesium deficit before operation. In another patient, diagnosis was made during operation and MgSO4 provided satisfactory control of the crisis. Catecholamine release was studied in five patients and MgSO4 was found to reduce catecholamine concentrations from the time of induction until tumour handling.
The influence of pre-operative treatment with the alpha-adrenoceptor blocking agent, phenoxybenzamine, on the incidence of adverse cardiovascular reactions during anaesthesia and surgery for phaeochromocytoma was evaluated in a series of 62 patients. Fifty-one of them received pre-operative treatment with phenoxybenzamine and eight of these were also treated with beta-adrenoceptor blocking agents. The median final daily dose of phenoxybenzamine was 160 mg and the median period of treatment 23 days. The evening before surgery and in the early morning on the day of surgery, intravenous infusion of phenoxybenzamine was given to 42 of the patients. Eleven patients operated on between 1956 and 1963 received no specific pre-operative treatment and served as a reference group. The alpha-adrenoceptor blocking treatment resulted in a considerably smoother peroperative course, as evidenced by a statistically significant reduction in the incidence of excessive blood-pressure variations. The blockade was not complete since 69% of the patients had systolic peaks greater than 175 mmHg during surgery. Pre-operative blood transfusions did not significantly affect the incidence of hypotensive episodes. Pre-operative beta-adrenoceptor blockade did not reduce the incidence of peroperative arrhythmia. On the basis of our experience, we recommend that all phaeochromocytoma patients be treated pre-operatively with alpha-adrenoceptor blocking agents.
The intraoperative management of the hyperadrenergic state associated with pheochromocytoma presents a formidable anesthetic challenge. The development of new and effective pharmacotherapy has allowed better control of the hemodynamic changes that can occur during this type of surgery. We report a case in which the short-acting β-blocker esmolol was of benefit in perioperative management of pheochromocytoma. To our knowledge this represents the first reported use of this agent in this condition.
The management of a patient with an unusual combination of anaesthetic problems, namely phaeochromocytoma and difficult intubation is described. Angiotensin II is discussed in the management of hypotension after excision of the tumour.
M-mode and 2-dimensional echocardiography were used to study 26 consecutive, unselected patients with pheochromocytoma over a 3-year period. Only 1 patient had congestive heart failure; more than half had no cardiac symptoms or abnormalities. The most common (80% of patients) echocardiographic pattern was normal left ventricular (LV) mass with normal or even increased systolic performance. When LV mass was increased, LV systolic function was either normal or only borderline depressed in most of the patients. Patients with echocardiographic LV hypertrophy had symmetric thickening of ventricular walls; no case of asymmetric septal hypertrophy was found. There was no correlation between 24-hour urinary norepinephrine excretion and any of the echocardiographic variables studied. In some patients, increased LV wall thicknesses did not correlate with increased LV mass as calculated by the Woythaler echocardiographic method. Left atrial enlargement was not seen in any patient, including those with increased LV mass. The electrocardiogram and echocardiogram may be discordant: Electrocardiographic LV hypertrophy was seen in 6 patients, of whom 5 had normal echocardiographic LV mass. In patients with pheochromocytoma who have no cardiac symptoms or other clinical evidence of cardiac involvement, echocardiographic findings are usually normal.
The management of five patients with phaeochromocytoma undergoing surgical removal is described. Pre-operative preparation with phenoxybenzamine and nifedipine for 7 days before surgery prevented excessive fluctuations in cardiovascular parameters in the peri-operative period and resulted in an uneventful recovery.
Severe hypoglycemia with delayed emergence occurred in a 12-yr-old boy following bilateral adrenalectomy for pheochromocytoma. Hypoglycemia after resection of pheochromocytoma may be due to release of insulin from the beta cells of the pancreas due to sudden withdrawal of catecholamines. Beta blockade with the use of propranolol impairs both hepatic glucose production and glucagon secretion mechanism. For early detection and treatment of hypoglycemia, perioperative blood glucose monitoring is important in patients undergoing adrenalectomy for pheochromocytoma.
This report describes the use of diltiazem to control circulatory fluctuations during anaesthesia in five patients undergoing
resection of a phaeochromocytoma. Diltiazem was administered continuously i.v. before anaesthesia and during surgery until
the draining vein from the tumour had been ligated. Arterial pressure and systemic vascular resistance decreased in association
with the infusion of diltiazem. Heart rate was stable, and there was no ventricular tachyarrhythmia. Arterial pressure was
controlled easily during the manipulation of the tumour, and there were no hypotensive episodes after the removal of the tumour.
Severe hypoglycaemia as a complication of excision of a phaeochromocytoma has been reported seven times in the world literature. The eighth case, reported here, is unusual for the severity of the hypoglycaemic neurological damage which persisted for 10 weeks before ultimate recovery.
Unless patients harbouring this uncommon tumour are correctly prepared and protected from the effects of excessive catecholamine release, they are greatly at risk when undergoing surgical procedures of any kind. This short review describes the clinical syndromes associated with phaeochromocytoma, the diagnostic procedures which may identify and localize the tumour(s), the principles and practical aspects of pharmacological control, and a method of anaesthetic management which has proved safe and effective in many patients.
Recently, an inhibitory dopaminergic receptor has been described that modulates catecholamine release from adrenal medulla. It has also been reported that low doses of droperidol increase arterial pressure in some patients with pheochromocytoma. The authors investigated whether an effect of droperidol on such a receptor could be one of the mechanisms involved in the hypertensive response. Isolated cat adrenal glands were perfused with Krebs-bicarbonate solution, and the catecholamine release was measured in the effluent. Then, the glands were stimulated by activation of the nicotinic receptor (nicotine, 5 microM), and the effect of low and high doses of droperidol and/or apomorphine on the catecholamine secretory responses evoked by nicotine was investigated. Low concentrations of droperidol (0.05 microM) (a dopaminergic antagonist) markedly increased the secretory response induced by nicotine whereas higher concentrations (50 microM) decreased it. Apomorphine (1 microM) (a dopaminergic agonist) inhibits the catecholamine release produced by nicotine, and this inhibitory effect was completely reversed by the lowest concentration of droperidol but not by the highest. In fact, the high concentration of droperidol further inhibited the catecholamine release induced by nicotine. The results suggest that the hypertensive responses evoked by low doses of droperidol in some patients with pheochromocytoma could be due to the inactivation of a dopaminergic inhibitory system present in the adrenal medulla that, under physiologic conditions, limits the amount of catecholamines released by the gland. Such as an inhibitory mechanism could operate in an exaggerated manner in patients with pheochromocytoma.
The study was undertaken to determine whether droperidol had an effect to induce catecholamine efflux from the adrenal medulla as a mechanism for the possible pressor effect of droperidol in patients with pheochromocytoma and, if so, to ascertain the site of action of this compound. The efflux of catecholamines from perfused dog adrenals was increased from control level, 0.15 micrograms/min, to 0.66 micrograms/min by the administration of droperidol 6.6 microM. This effect of droperidol was not dependent on extracellular Ca++, in contrast to acetylcholine. The concomitant secretion of catecholamines and dopamine-beta-hydroxylase was observed in response to acetylcholine and caffeine. However, droperidol-, histamine-, and reserpine-induced catecholamine efflux was not accompanied by dopamine-beta-hydroxylase release. In additional studies, chromaffin granules were isolated with a Millipore filter technique from the bovine adrenal medulla and were incubated for 10 min in an isotonic medium to examine the direct effects of droperidol. Droperidol did not enhance the efflux of catecholamines from the granules in contrast to histamine. The uptake of 14C-norepinephrine into the granules was inhibited by droperidol in a manner comparable to reserpine. The results suggest that droperidol induces catecholamine efflux from adrenal medullary cells and the efflux probably is caused by a nonexocytotic mechanism. A contributing mechanism was an inhibition of catecholamine uptake into chromaffin granules, resulting in an increased diffusion of catecholamines out of the cell.
Ten patients with pheochromocytoma underwent preoperative acute volume loading to determine whether fluid infusion severely increased pulmonary capillary wedge pressure without improving forward flow, and to provide a guide for intraoperative volume replacement. In one patient, volume loading confirmed baseline pressure data suggesting a discrepancy between right and left ventricular filling pressures. In a second patient with normal baseline wedge pressure, volume loading revealed an unsuspected ventricular dysfunction. During subsequent surgery, both volume and speed of fluid infusion were adapted to the preoperative ventricular response.
Virtually all patients undergoing resection of a phaeochromocytoma exhibit hypertensive crises at some period perioperatively. In order to study the events associated with hypertensive responses, cardiovascular variables were measured with a Swan-Ganz pulmonary artery catheter and plasma catecholamine levels were determined simultaneously in eight patients during surgery for phaeochromocytoma. Hypertensive responses requiring vasodilator treatment occurred in five patients, i.e. systolic blood pressure (BP) greater than 200 mmHg for more than 1 min. Transient elevation, at least in systolic BP, to greater than 200 mmHg occurred in all patients. Hypertensive responses were identified associated with two circumstances: the first in association with noxious stimuli, i.e. intubation, skin incision, etc., but were not generally accompanied by an elevation in plasma noradrenaline and adrenaline levels; the second occurring during tumour manipulation were more severe and were always accompanied by elevated plasma noradrenaline and adrenaline levels. Transient left ventricular dysfunction, defined by increased pulmonary capillary wedge pressure (PCWP) and decreased cardiac index (CI) secondary to a marked increase in systemic vascular resistance (SVR), was observed in four patients during palpation of the tumour, while one patient exhibited more marked and prolonged ventricular dysfunction. It is concluded that hypertensive responses associated with noxious stimuli may be controlled with deep anaesthesia while those due to tumour manipulation cannot be prevented and are best treated with vasodilators.
The effects of alternate day and daily prednisone on leukocyte kinetics were studied in 20 patients with inflammatory diseases to investigate the mechanisms of corticosteroid induced susceptibility to infections. With daily prednisone, neutrophil and monocyte inflammatory responses were significantly decreased. In patients on alternate day prednisone, who were studied during the day on which prednisone was administered, neutrophilia and monocytopenia occurred, and cutaneous inflammatory responses of monocytes, but not of neutrophils, were significantly reduced. On the day of therapy of alternate day prednisone and with daily therapy, the half life of labeled blood neutrophils was significantly prolonged, and the prolongation was proportional to the dose of the drug given. In contrast, in patients maintained on alternate day prednisone therapy and studied on the day off drug, leukocyte counts, inflammatory responses and neutrophil half life were normal.
A 44-year-old woman with hypertrophic cardiomyopathy and a noradrenaline-secreting phaeochromocytoma is described. She experienced as great improvement in cardiovascular symptoms during double-blind treatment with the calcium-channel blocker nifedipine compared with the placebo period. Symptom relief on nifedipine therapy was associated with a pronounced decline in elevated urinary noradrenaline levels. This observation suggests that calcium-channel blockers interfere with the release of noradrenaline from phaeochromocytoma tissue and thus may be beneficial in patients with phaeochromocytoma.
THE early diagnosis of pheochromocytoma is important, not only because it offers the possibility of curing hypertension but also because unrecognized pheochromocytoma is a potentially lethal condition. Hypertensive crisis or shock or both leading to death have been precipitated by drugs, anesthetic agents, parturition, or surgery for an unrelated condition. Moreover, 8 to 10 per cent of the tumors are malignant. The detection of pheochromocytoma requires a high degree of clinical alertness. Although rare cases have been reported in which the tumor was not associated with hypertension, especially in patients with familial tumors, elevation of blood pressure, either continuous or . . .
Phaeochromocytoma may simulate any hypertensive syndrome. Although it is an uncommon cause of high arterial pressures, its recognition is important because of serious anaesthetic problems if the diagnosis is missed before any surgical procedure. Preoperative preparation with alpha- and beta-adrenergic blocking drugs is recommended by most authors, although no controlled study has been undertaken regarding their efficacy in the prevention of intraoperative cardiovascular disturbances. It should be mentioned that, in expert hands, the operative mortality does not appear to have been influenced by preoperative alpha- and beta-adrenergic blockade. However, preoperative therapy is mandatory in patients with sustained or paroxysmal hypertension. In these patients, prazosin was effective in our recent experience. Virtually all anaesthetic agents and techniques have been used successfully and the choice of a specific agent is of secondary importance. The depth of anaesthesia is more important, since it can inhibit adrenergic and cardiovascular responses to noxious anaesthetic and surgical stimuli. The major factor responsible for reduction in operative mortality is control of hypotension by fluid replacement rather than by use of catecholamines following removal of the phaeochromocytoma.