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On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.58 no.2 Campinas Mar./Apr. 2008
Anesthesia in a patient with multiple endocrine abnormalities. Case report
Anestesia para paciente portadora de múltiples afecciones endocrinas. Relato de caso
Renato Toledo MacielI; Fátima Carneiro Fernandes, TSAII; Leonel dos Santos Pereira, TSAIII
do CET/SBA Bento Gonçalves, HUCFF-UFRJ
IICo-Responsável pelo CET/SBA Bento Gonçalves, Professora Adjunta, Doutora em Anestesiologia, UFRJ
IIIChefe do Serviço de Anestesiologia do HUCFF-UFRJ; Co-Responsável pelo CET/SBA Bento Gonçalves; Professor Adjunto, Doutor em Anestesiologia, UFRJ
OBJECTIVES: Insulinoma is the most common pancreatic endocrine tumor and
it can be associated with multiple endocrine neoplasia (MEN). This is a report
on a patient with multiple endocrine abnormalities, who did not fulfill the
criteria of known syndromes (MEN) and the clinical-anesthetic particularities
that influenced the anesthetic management.
CASE REPORT: A 23-year old female patient with episodes of hypoglycemia difficult to control, associated with Cushing's disease and prolactinoma without symptoms of pituitary compression and with normal thyroid and parathyroid. Investigation found a retroperitoneal mass of unknown origin which in face of the clinical presentation raised the hypothesis of insulinoma. The patient also referred to be a Jehovah's Witness. Biopsy of the mass by videolaparoscopy and enucleation of the insulinoma were proposed. On physical exam the patient was overweight, had protruding teeth, she was classified as Mallampati 3 and had symptoms of sleep apnea. Laboratorial exams revealed hematocrit 58%. Pre-anesthetic medication consisted of oral midazolam (7.5 mg) and clonidine (200 µg). Fentanyl (150 µg), clonidine (90 µg), propofol (150 mg) and pancuronium (8 mg) were used for anesthetic induction and she was intubated without intercurrences. Central venous access and invasive blood monitoring were instituted. Intravenous infusion of D5W with electrolytes was instituted and capillary glucose levels were monitored every 30 minutes, which did not demonstrate any episodes of hypoglycemia during the surgery. The patient remained hemodynamically stable even during the pneumoperitoneum. She developed postoperative episodes of hypoglycemia, which motivated the re-operation.
CONCLUSIONS: This case is unique due to the presence of multiple endocrine abnormalities and the particularities of the surgical-anesthetic management. Intraoperative monitoring is mandatory during removal of an insulinoma to avoid incomplete tumor resection. Multiple challenges in one patient demand the knowledge, by the anesthesiologist, of each obstacle and its interactions in order to devise strategies to control them.
Key Words: DISORDERS, Endocrine: insulinoma, hypoglycemia, multiple endocrine syndrome, Cushing's disease, prolactinoma, polycythemia.
Y OBJETIVOS: El insulinoma es un tumor endocrino pancreático más
común. Pude estar asociado a neoplasias endocrinas múltiples (NEM).
Se ha relatado el caso de paciente con disturbios endocrinos múltiplos
que, sin embargo, no se encuadra en síndromes (NEM) ya conocidas, y con
particularidades clínico anestésicas que influyeron en el manejo
de su anestesia.
RELATO DEL CASO: Paciente femenina, 23 años, con hipoglicemias de difícil control asociadas a la enfermedad de Cushing y prolactinoma, sin síntomas compresivos hipofisarios, y con estudios de tiroides y de paratiroides sin alteraciones. La investigación laboratorial encontró masa retroperitoneal de etiología desconocida que, relacionada con la situación clínica, conllevó a la hipótesis de insulinoma. Decía que era testigo de Jeová. La propuesta terapéutica era biopsia de la masa por videolaparoscopía y enucleación del insulinoma. Cuando se le hizo el examen, se le encontró obesa, con dientes protuberantes, Mallampati 3 y síntomas de apnea obstructiva del sueño. En los exámenes laboratoriales, el resultado relevante fue el hematócrito de 58%. Recibió midazolan (7,5 mg) y clonidina (200 µg) vía oral, como medicación preanestésica. La inducción anestésica fue realizada con fentanil (150 µg), clonidina (90 µg), propofol (150 µg) y pancuronio (8 mg), siendo realizada la intubación traqueal sin problemas. Se establecieron el acceso venoso central y el monitoreo invasivo de la presión. Se mantuvo infusión de glicosis al 5% con electrolitos y se monitoreó la glicemia capilar a cada 30 minutos, que no mostró episodios de hipoglicemia durante la operación. Se mantuvo hemodinámicamente estable incluso durante el neumoperitoneo. En el postoperatorio presentó episodios de hipoglicemia, que motivaron su reoperación.
CONCLUSIONES: La singularidad del caso está en la conjunción de las múltiples endocrinopatías y de particularidades del manoseo quirúrgico-anestésico. La exéresis del insulinoma debe ser monitoreada en el intraoperatorio para que se eviten resecciones incompletas del tumor. La multiplicidad de los desafíos en un solo paciente exige del anestesiólogo el conocimiento de cada obstáculo y sus interacciones, trazando estrategias para solucionarlos.
Patients with endocrine-metabolic disorders represent a challenge for the anesthesiologist regarding preoperative management and care during the anesthetic-surgical procedure. This is the report of a young patient, Jehovah's Witness, with insulinoma, prolactinoma and Cushing's disease with an adrenal mass of unknown etiology, undergoing videolaparoscopy.
The presence of multiple factors that, when combined interfere with several organs and systems influencing the anesthetic management makes this case unique.
The international literature stresses the preoperative management of multiple endocrine neoplasias in the form of a few reports and revisions, which were used to compare with the present case, although the patient did not fulfill the criteria for any of those disorders because she did not have thyroid or parathyroid compromise. The approach of a patient with insulinoma was emphasized, since this was the main reason for the surgery at the time.
A 23-year old female patient, 1.63 m, 103 kg, BMI = 38.76 kg.m-2, admitted for repeated episodes of hypoglycemia attributed to an insulinoma in the head of the pancreas and also for having a retroperitoneal mass close to the left adrenal gland of unknown etiology, but with negative studies for pheochromocytoma. The surgical management proposed included resection of the pancreatic tumor and biopsy of the mass by videolaparoscopy.
The patient also had a pituitary macroadenoma that produced prolactin and ACTH, with classical stigmata of hypercortisolism, such as centripetal obesity, gibbosity, acanthosis nigricans, violacious striae, hypertension, acne and hirsutism (Figure 1). The patient did not have any signs of cranial nerve compression. Laboratorial studies of the parathyroid were normal. She had a history of seizures related with the episodes of hypoglycemia. She rejected blood transfusion on religious grounds.
Her airways were classified as Mallampati 3, having protruded teeth, short neck and symptoms suggestive of sleep apnea as complicating factors for ventilation and intubation (Figure 2).
Her medications included captopril, bromocriptine, verapamil and valproic acid. Blood tests were all within normal limits but for a hematocrit of 58%, with normal erythropoietin levels and arterial blood gases. On preoperative evaluation, she was classified as ASA III and received oral midazolam, 7.5 mg, and clonidine, 200 µg as pre-anesthetic medication.
The patient was admitted to the operating room on stage Ramsay 3; a peripheral venous access was established and initial monitoring included cardioscope (DII and V5 derivations), pulse oximeter and non-invasive blood pressure. Using the technique of Seldinger the right subclavian vein was catheterized with a 7F double-lumen catheter and the radial artery was catheterized to record MAP. After oxygenation, anesthesia was induced with 150µg of fentanyl, 90 µg of clonidine, 150 mg of propofol and 8 mg of pancuronium. The patient was intubated without intercurrences with visualization Cormack-Lehane 1. Anesthesia was maintained with N2O/O2/isoflurane in a circular system with controlled mechanical ventilation.
Capillary glucose levels were checked every 30 minutes varying from 79 to 129 mg.dL-1. Infusion of D5W with electrolytes was titrated according to test results. There were no episodes of hypoglycemia during the procedure. The surgeons decided not to approach the retroperitoneal mass.
At the end of the surgery, the neuromuscular blockade was reversed and the patient was extubated without intercurrences. The final hematocrit was 47%. The patient was awake when she was transferred to the ICU, with SpO2 98% and with nebulization set at 5 L.min-1 O2.
Since the patient still had episodes of hypoglycemia she was re-operated and other pancreatic insulinomas were resected but during her follow-up she remained without absolute control over the hypoglycemic episodes.
Revisions on the anesthetic management of patients with isolated endocrinopathies are frequent 1,2. On the other hand, the management of multiple glandular disorders in the same individual is less common forcing the anesthesiologist to work with the particularities of each situation accumulated in the same patient3.
The case presented here does not fulfill the criteria for any of the multiple endocrine neoplasia because she had normal thyroid and parathyroid function 3. Insulinoma is a tumor of beta-pancreatic cells that produce insulin, which can cause severe hypoglycemia 3,4 associated with elevated concentrations of a byproduct of endogenous insulin secretion, the C peptide 5. Hypoglycemic manifestations are related with exacerbation of the activity of the sympathetic nervous system, causing tachycardia, palpitations and/or diaphoresis. In the central nervous system, the reduction in blood glucose levels, secondary to hyperinsulinemia, causes symptoms that vary from headache to seizures. Frequently, episodes of mental confusion are mistaken for psychiatric disorders delaying diagnosis and treatment 6.
Fasting increases the risk of preoperative hypoglycemia and for this reason the administration of D5W or D10W starting the night before surgery is recommended 5-7. The infusion can be maintained during the surgery or interrupted up to 2 to 3 hours before the incision 5,7. The use of "artificial pancreas", which by monitoring blood glucose levels is capable of infusing insulin or glucose and has been already used in similar circumstances 8 has its limits by elevated cost.
Frequent monitoring of blood glucose levels is necessary during resection of an insulinoma 9. Hypoglycemic symptoms, such as tachycardia and diaphoresis can be interpreted as the superficial plane of anesthesia and delay in treatment can in extreme conditions cause lesions in the central nervous system 10. The increased release of insulin coincides with the periods of tumor manipulation 3,6. Measurements every 10 to 15 minutes are recommended to maintain safe blood glucose levels 7,9. In the case presented here, blood glucose levels were verified every 30 minutes, which apparently was adequate. Signs of sympathetic hyperactivity, especially after tumor manipulation, justify repeated determinations of blood glucose levels to avoid the risk of severe hypoglycemia.
The anesthetic technique should use agents that reduce brain metabolism and consequently oxygen consumption. Maintenance of normocapnia is recommended 3. Inhalational anesthetics reduce the release of insulin and in theory their use is advantageous in those patients. However, this superiority has not been clinically proven 11.
Twelve percent of the patients are re-operated 12 probably because they have multiple or very small tumors 7. Therefore, it is necessary to know intraoperatively whether the excision was complete. Shortly after removal of the tumor, blood glucose levels tend to increase 5 but this does not mean surgical success 13. Intraoperative ultrasound also has a low accuracy 14. Insulin blood levels after selective catheterization of pancreatic veins and arterial stimulation with calcium to release the hormone seems to be a reliable method to localize residual tumors in the operating room 7,15. In the case presented here, re-operation was necessary despite histopathological confirmation of insulinoma.
Cushing's disease caused by increased production of ACTH and hyperstimulation of the adrenal cortex causes metabolic, hemodynamic, respiratory, immunological and hematological changes 1,16. Hirsutism, centripetal obesity, acne and a hump on the posterior neck are frequently found.
Accentuated elevation of cortisol aggregates mineralocorticoid effects to its metabolic actions. Due to sodium retention the circulating volume and elimination of potassium are increased contributing to the hydro-electrolytic imbalance and hypertension. The development of hypertension has other pathophysiological mechanisms involving vascular reactivity and production of prostaglandins, responsible for changes such as ventricular hypertrophy that result in diastolic dysfunction and increase myocardial oxygen consumption 16,17. Although the blood pressure of the patient presented here was under control with medication, the choice of clonidine as pre-anesthetic medication was done to guarantee intraoperative equilibrium of the blood pressure. However, fluctuation of blood glucose levels was also affected demanding closer monitoring.
Glucose intolerance occurs in at least 60% of patients with Cushing's syndrome with several cases of frank diabetes mellitus 16,18. Currently, although there are no scientific studies that include all types of patients there is growing evidence that intraoperative control of blood glucose levels with intravenous infusion of insulin reduces morbidity and mortality of surgical patients 19,20. In the patient presented here, control of blood glucose levels and metabolic control was paramount because she had other endocrinopathies that although they had opposing effects they could alter significantly her survival.
Sleep apnea is more frequent in patients with Cushing's, being secondary to the associated obesity and/or myopathy and can be aggravated by the pre-anesthetic medication 21-23. Therefore, the probability of difficult airways for ventilation and/or intubation was increased 24.
Osteoporosis, present in up to 50% of patients with hypercortisolism associated with hyperprolactinemia, which reduces bone density, increases the risk of fractures during manipulation and positioning in the operating table 16,25.
The elevated preoperative hematocrit represented a risk since hyperviscosity could be associated with blood stasis favoring thromboembolic events especially in patients under pneumoperitoneum in whom blood flow to the lower limbs is reduced 26,27. On the other hand, the elevated hematocrit in a Jehovah's Witness allowed foregoing especial techniques to avoid blood transfusion since the potential for hemorrhage during the surgery was small.
Peripheral venous access in those patients can be difficult due to the combination of obesity and skin changes 1,16. They are also more susceptible to bleeding 6 and catheterization of a deep vein allows monitoring saturation and central venous pressure (CVP), although this measurement does not have correlation with left ventricular end-diastolic volume or with improvement of cardiac output after infusion of volume 28,29. Pneumoperitoneum increases the CVP, decreasing its importance as an indicator of volume replacement 26.
Catheterization of the radial artery was aimed at the continuous monitoring of the blood pressure and to facilitate serial blood drawing in a patient that could have cardiological complications, hypovolemia and electrolyte imbalances.
Success managing patients with endocrinopathies is strictly connected with maintenance of the endocrine balance and with the systemic repercussions that oscillations might cause. The association of multiple disorders as in the present case multiplied the problems to be avoided.
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Dra. Fátima Carneiro Fernandes
Av. Sernambetiba, 2930/304, Bloco 4 Barra da Tijuca
22620-172 Rio de Janeiro, RJ
Submitted em 26
de março de 2006
Accepted para publicação em 18 de dezembro de 2007
* Received from Hospital Universitário Clementino Fraga Filho da Faculdade de Medicina da Universidade Federal do Rio de Janeiro (HUCFF-UFRJ), Rio de Janeiro, RJ