Anesthetic management of two patients with insulinoma using propofol--in association with rapid radioimmunoassay for insulin

We experienced anesthetic management of two patients with insulinoma in whom frequent hypoglycemic episodes with blood glucose levels of 39-42 mg.dl-1 had been observed. Each patient received epidural analgesia with a catheter inserted at the T 9/10 intervertebral space. Anesthesia was induced with propofol 80-100 mg and fentanyl 200 micrograms. Tracheal intubation was facilitated with vecuronium 6 mg. Anesthesia was maintained with continuous infusion of propofol and epidural anesthesia. Rapid measurements of immunoreactive insulin (IRI) were useful for localization of insulinoma during surgery. Perioperative plasma glucose levels could be maintained within normal ranges by continuous infusion of glucose. Rebound hyperglycemic episodes were not observed, and IRI was reduced after removal of the insulinoma. General anesthesia using propofol and epidural block is a useful choice for the anesthetic management of patients undergoing an operation for removal of an insulinoma.     

Glucose management in patients undergoing operation for insulinoma removal

Medical records of 38 patients undergoing anesthesia and surgery for removal of an insulinoma were reviewed to determine 1) the safety of avoiding intraoperative glucose, 2) the appropriate frequency of plasma glucose analysis, and 3) the accuracy of using rebound hyperglycemia as an indication of tumor removal. Plasma glucose was determined approximately every 15 min during operative and recovery-room periods. The changes in plasma glucose concentrations before tumor removal were compared with those occurring after the resection in each patient by separate linear regressions of glucose concentration versus time. The slopes of the preresection regression lines averaged +0.196 (+/- SD 0.577) mg X dl-1 X min-1. The mean of the postresection slopes was +0.624 (+/- SD 0.339) mg X dl-1 X min-1. The mean difference in slope (post- minus pre-) was +0.426 (+/- SD 0.748) mg X dl-1 X min-1, indicating that a significant (P less than 0.02) increase in post-resection slope had occurred. In no case did a preresection plasma glucose concentration decrease to less than 50 mg X dl-1 if the previous value had been 60 mg X dl-1 or greater. Nonetheless, there were nine patients whose plasma glucose did decrease to less than 50 mg X dl-1 at some time during the operative course. Only 39% of patients showed a rebound of 20 mg X dl-1 or more in the first 30 min after resection. The authors conclude that intermittent sampling is safe as long as plasma glucose is kept above 60 mg X dl-1 by infusing glucose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood glucose control by an artificial endocrine pancreas in a patient with phaeochromocytoma

In a patient with phaeochromocytoma who presented with unstable diabetes mellitus, an artificial endocrine pancreas was used intraoperatively. Anaesthetic agents included enflurane, nitrous oxide and oxygen. Nicardipine was used to control hypertensive episodes. The initial blood glucose concentration was 173 mg X dl-1 and it decreased to 110 mg X dl-1 in response to insulin infusion, but plasma catecholamines were markedly increased. Seventy minutes later, the glucose concentration increased progressively to 249 mg X dl-1 despite massive insulin infusion, maximally 5.64 mU X kg-1 X min-1. The blood glucose concentration reached a peak at the time of the ligation of the venous drainage from the tumour and the peak was coincident with that of plasma catecholamine levels (epinephrine: 20.8 ng X ml-1, norepinephrine 16.4 ng X ml-1). Both glucose and catecholamine concentrations decreased promptly after removal of the tumour and hypotension followed likely because of a persistent vasodilatatory effect of nicardipine. The profiles of blood glucose, insulin and glucose infusion rates provided by the artificial endocrine pancreas suggested that the insulin resistance began to be reversed shortly after removal of the phaeochromocytoma.     

Role of intraoperative insulin monitoring in surgical management of insulinoma

BACKGROUND AND PURPOSE: Precise localization and surgical excision is the therapeutic strategy for insulinomas. However, it is often difficult to localize the insulinomas, because of their small size. Surgeons may not localize and remove all of them together, particularly in patients with multiple insulinomas. We reviewed our experience to confirm the efficacy of blood glucose and intraoperative immunoreactive insulin (IRI) monitoring for surgical management of insulinomas. PATIENTS AND METHODS: Thirty-nine patients with insulinoma were surgically treated in our department. Perioperative blood glucose monitoring was performed in 14 patients, intraoperative quick IRI assay of the peripheral blood in 10 patients, and assay of a portal sample in 4 patients by an IMX analyzer. RESULTS: Rebound response of blood glucose to insulinoma removal was not always noted (8/14; 57%). Seven of ten patients showed a decrease of peripheral serum IRI levels within 15 minutes after removal of the insulinoma. The other two patients showed a rebound response of peripheral blood glucose or portal IRI. All the patients who had intraoperative monitoring of peripheral blood and peripheral and portal IRI had no recurrent insulinoma syndrome after surgical removal of their insulinomas. CONCLUSION: Combined monitoring of peripheral blood glucose and peripheral and portal IRI are helpful in the surgical management of insulinomas, as they can indicate that no insulinoma remains.     

An islet cell carcinoma containing glucagon and insulin. Chronic glucagon excess and glucose homeostasis.

Described here is a patient who had an islet cell carcinoma containing both glucagon (glucagonoma) and insulin (insulinoma). Complete removal of the tumor was possible. Immunoreactive glucagon (IRG) could be extracted from all parts of the tumor (approximately 50 mug./gm.) and was shown to be fully bioactive. Immunoreactive insulin (IRI) could be extracted only from one section of the tumor (approximately 30 mug./gm.). The clinical and biochemical manifestations of the disease were dermatitis, diabetes, weight loss, anemia, hypoaminoacidemia, and hyperketonemia. The diabetes was characterized by low or normal fasting blood glucose concentrations and by impaired glucose tolerance (Kg = 0.4). After complete removal of the tumor, the dermatitis cleared, the catabolic state changed into an anabolic state, blood amino acid concentrations increased, and blood ketone-body concentrations decreased. Fasting blood glucose concentrations, however, rose above 200 mg./dl., and glucose tolerance declined further (Kg = 0.15). Hourly blood sampling for 24 hours, intravenous and oral glucose tolerance tests, intravenous arginine and tolbutamide tolerance tests with serial determinations of IRG, IRI, and blood glucose were performed preoperatively and again two weeks and two months postoperatively. The results of these studies demonstrated marked abnormalities in the stimulation and suppression of glucagon and insulin release. In addition, they failed to demonstrate a glycemic effect on the chronically elevated glucagon concentrations in this patient, while identifying insulin as the dominant factor determining blood glucose homeostasis.     

Insulinoma: Selective arterial calcium injection performed to confirm localization and complete resection

A case of insulinoma is reported in a patient in whom selective arterial calcium injection (SACI) tests were performed both to confirm tumor localization before surgery and to confirm complete tumor removal during surgery. An 18-year-old woman with hypoglycemic episodes was diagnosed with an insulinoma in the pancreatic body demonstrated by celiac arteriography. In a preoperative SACI test, calcium was injected into the splenic artery (SpA), gastroduodenal artery (GDA), and superior mesenteric artery (SMA). Serum immunoreactive insulin (IRI) and proinsulin levels were measured in hepatic venous samples. IRI was markedly increased after the injection of calcium into the GDA and SMA, while there was no response in IRI levels when calcium was injected into the SpA. Therefore, no occult insulinoma was revealed in the distal area fed by the SpA, although the presence of insulinoma was uncertain in the proximal pancreas. In the intraoperative SACI test, calcium was injected into the celiac artery. Insulin (determined by enzyme immunoassay) and proinsulin levels were measured in portal venous samples before and after resection of the tumor. After resection, these levels decreased in response to the calcium stimuli, confirming complete removal of the insulinoma. The SACI test was helpful to localize the insulinoma and was useful to confirm the complete removal of the tumor.     

The insulin sensitivity index in nondiabetic man. Correlation between clamp-derived and IVGTT-derived values

Although the minimal-model-based insulin sensitivity index (S1) can be estimated from the results of a simple 180-min intravenous glucose tolerance test (IVGTT), its relationship to widely accepted but technically more difficult clamp-based techniques has not been resolved in humans. Therefore we measured S1 by standard IVGTT, modified IVGTT, and clamp methods in 10 nondiabetic men with %IBW of 109 +/- 12 (mean +/- SD). In the euglycemic clamp studies, insulin was infused to bring insulin levels (IRI) from basal, 8 +/- 4 microU/ml, to plateaus of 21 +/- 5 and 35 +/- 6 microU/ml. S1[clamp], measured as the increase in glucose (G) clearance per increase in IRI [delta INF/(delta IRI X G)], averaged 0.29 +/- 0.09 ml/kg X min per microU/ml. In the IVGTT studies, 300 mg/kg G was given as an i.v. bolus, and G and IRI were measured for 180 min; in the modified (mod) IVGTT, tolbutamide (300-500 mg) was given i.v. 20 min after the G to observe the effect of an IRI peak on G removal after G level was free of initial "mixing" effects. The S1 estimated by computer did not differ significantly between standard [(6.9 +/- 3.4) X 10(-4) min-1 per microU/ml] and modified [(6.7 +/- 3.5) X 10(-4) min-1 per microU/ml] tests, indicating no bias due to the differing insulin patterns and levels. There was a strong positive correlation between S1 (mod IVGTT) and S1(clamp): r = 0.84; N = 10; P less than 0.002. The correlation between S1(standard IVGTT) and S1(clamp) was 0.54, suggesting the modified test is less "noisy." Nonetheless, in eight euglycemic women with a wider range of adiposity, S1(standard IVGTT) has been significantly correlated with %IBW (r = -0.72) and basal IRI (r = -0.84). The correlation between S1 measures by clamp and IVGTT methods provides one step toward validation of the minimal model for studies of insulin action in man.     

Rebound hyperglycemia and peroperative normalization of insulinemia. Complete excision of insulinoma?]

Clinical usefulness of the hyperglycemic rebound and the normalization of plasma insulin level as intraoperative markers of complete removal of insulinoma was assessed. Surgical removal was curative (no clinical or biological recurrence) in six patients harboring a single adenoma (mean follow-up = 32.2 months). In these patients plasma glucose increased an average of 32 mg/dl 30 minutes after resection, 68 mg/dl after 60 minutes, and 91 mg/dl after 90 minutes. Sensitivity of hyperglycemic rebound (defined as a plasma glucose increment of at least 30 mg/dl after tumor removal) as a marker of complete resection of the insulinoma was 40% at 30 min and 83% at 60 minutes after resection. Preresectional values of plasma immunoreactive insulin were elevated in 3 out of 4 patients with adenoma. All postresectional values were within normal ranges. Two patients operated on because of malignant insulinoma, underwent partial tumor resection; hyperglycemic rebound was also present, and high preresectional insulin values became normal 30 minutes after partial tumor removal. We conclude that information provided by intraoperative monitoring of both plasma glucose and insulin cannot be used as the only markers of complete resection of all insulinomas. Only long term clinical and biological follow-up can guarantee the complete resection of an insulinoma.     

Repeated postoperative hypoglycemia in a woman with multiple pheochromocytomas]

A case of repeated postoperative hypoglycemia following removal of multiple pheochromocytomas in a non-diabetic 23-year-old woman is presented. Although the hypoglycemia did not occur after the first operation, it was recognized after the second and third operations. The blood sugar levels were 54 mg.dl-1 and 25 mg.dl-1, respectively, and continuous intravenous glucose infusion was necessary for about 15 hours postoperatively. This complication may be related to sudden withdrawal of catecholamines. Frequent monitoring of blood sugar level as well as cardiovascular system is important for perioperative management of pheochromocytoma.     

Sevoflurane anesthesia for pancreatectomy in an infant with nesidioblastosis

We report a case of nesidioblastosis, which is characterized by hyperinsulinism due to a diffuse increase in the number of beta-cells in the pancreas and, consequently, severe hypoglycemia. The patient was a 79-day-old boy. He had been suffering from severe hypoglycemia despite aggressive treatment, including glucose loading and administration of glucocorticoid and diazoxide. Pancreatectomy was performed. Anesthesia was induced by thiamilal 25 mg and vecronium and was maintained by 1 to 2% sevoflurane in 65% nitrous oxide and fentanyl 5 micrograms. No hemodynamic instability was observed during anesthesia. Blood glucose level was maintained around 200 mg.dl-1 without any hyperglycemic event by continuous infusion of 20% glucose at the rate of 14.5 mg.kg-1.min-1, which was calculated from the daily glucose demand to prevent hypoglycemia preoperatively.     

Anesthésie pour insulinome

The difficulties of interpretation of blood surgar level changes during the postoperative period in the anaesthetic management of insulinoma are discussed. Several specific means reduced the errors in the assessment of the hyperglicaemic rebound which occurred after the removal of the tumour. They consisted of continuous sugar infusion accorded to measured glucose levels, in order to maintain a constant blood sugar value between 50 and 70 mg · 100 ml⁻¹ before removal of the insulinoma. Furthermore, analgesia was provided by high doses of fentanyl. Sugar containing solutes were avoided during the procedure. Glucose levels rose slowly after tumour removal and reached 170 mg · 100 ml⁻¹ at 120 min. This rebound was known to be of no help in ascertaining complete resection. Simultaneous determinations of blood glucose and insulin were obtained. The value of portal blood insulin was found to be normal (12.3 mU · 1⁻¹) 30 min after insulinoma removal. Turner's index calculated every 30 min decreased simultaneously (143) and reached a normal value at 120 min (39). These results, obtained during the surgical procedure all the more easily because of rapid laboratory procedures, could be better arguments in determining whether tumour removal has been complete.     

Diagnostic monitoring of plasma levels of glucose and insulin during surgery for insulinoma

With serial measurement of blood sugar levels during surgery in three patients with solitary insulinoma, we confirmed the location, then later, the complete elimination of the insulin-secreting tumor. Following virgorous massage of the tumor, blood sugar levels decreased while the levels progressively increased within 20 min following removal of the tumor. Subsequent measurement of simultaneous plasma insulin levels provided further confirmation. Plasma levels of insulin increased in accordance with massage of the tumor. Prior to removal of the tumor, the levels progressively decreased to less than the preoperative levels. For success in detecting slight changes in blood sugar levels secondary to increase or decrease of insulin secretion during surgery for insulinoma, (1) controlled infusion of glucose to keep blood sugar levels around 80 mg/dl and (2) frequent rapid determination of blood sugar levels are considered to be important.     

Case of anaphylactic shock induced by an antibiotic after induction of anesthesia

We report a case of anaphylactic shock induced by an antibiotic administrated after induction. A 39-year-old man was scheduled for removal of right adrenal tumor. After insertion of an epidural catheter, anesthesia was induced with an intravenous bolus injection of fentanyl 100 microg, propofol 130 mg and vecuronium 6 mg. The trachea was intubated smoothly and anesthesia was maintained with sevoflurane. Sultamicillin tosilate was administrated intravenously. Soon, ephedrine 12 mg was given intravenously because his blood pressures decreased. However, his blood pressure did not recover, but fell down to 35/22 mmHg. He was turned to head-down position, and 100% oxygen was administrated. Following epinephrine 0.1 mg injection, his blood pressure increased to 80/40 mmHg. Epinephrine at 0.005-0.02 microg x kg(-1) x min(-1) was infused continuously to maintain his blood pressure. We found erhythemia on his face, shoulders and arms. Hydrocortisone sodium succinate and acetate Ringer's solution were administrated to treat his anaphylactic shock and the surgery was postponed. The blood samples indicated that this event was IgE-mediated anaphylactic reaction. From his past history, penicillin allergy was confirmed. The surgery was rescheduled and anesthesia was managed in the same way as previous one. Surgery was successfully performed using levofloxacin, which had been taken orally before induction of anesthesia.     

Postoperative profound hypoglycemia after resection of adrenaline-predominant pheochromocytoma

A 54-year-old woman was scheduled for resection of pheochromocytoma. Anesthesia was maintained with general anesthesia combined with thoracic epidural anesthesia. The blood glucose decreased to 30 mg x dl(-1) about four hours after the tumor resection, despite intravenous administration of glucose at a rate of 15 g x hr(-1) with intermittent boluses of 5 g of glucose. The blood glucose levels increased over 100 mg x dl(-1) with intravenous administration of 15 g x hr(-1) glucose, 6 hours after tumor resection.     

功能性胰岛素瘤的诊治(附12例)

目的 探讨功能性胰岛素瘤的诊治特点,提高对该病的认识.方法 回顾性分析2000年至2009年吉林大学中日联谊医院收治的12例功能性胰岛素瘤临床资料.结果 12例术前空腹血糖值和胰岛素阳性率分别为92%和89%,IRI/G和C-肽的阳性率达100%.术前腹部超声、CT和MRI定位诊断准确率分别是75%、36%和0%,而术中扪诊结合术中超声的定位准确率达100%.术中血糖监测,10例在肿瘤切除后1 h内血糖上升1倍以上,2例1.5 h后上升1倍以上.随访7例,均未再出现低血糖症状.3例胰瘘.结论 对疑有功能性胰岛素瘤的病例,除检测血糖、胰岛素外还应检测IRI/G、C-肽.术中扪诊及超声是肿瘤定位的有效手段.监测肿瘤切除后血糖变化,结合术中快速病理可判定肿瘤是否完全切除.     

功能性胰岛素瘤的诊治(附12例)

目的 探讨功能性胰岛素瘤的诊治特点,提高对该病的认识.方法 回顾性分析2000年至2009年吉林大学中日联谊医院收治的12例功能性胰岛素瘤临床资料.结果 12例术前空腹血糖值和胰岛素阳性率分别为92%和89%,IRI/G和C-肽的阳性率达100%.术前腹部超声、CT和MRI定位诊断准确率分别是75%、36%和0%,而术中扪诊结合术中超声的定位准确率达100%.术中血糖监测,10例在肿瘤切除后1 h内血糖上升1倍以上,2例1.5 h后上升1倍以上.随访7例,均未再出现低血糖症状.3例胰瘘.结论 对疑有功能性胰岛素瘤的病例,除检测血糖、胰岛素外还应检测IRI/G、C-肽.术中扪诊及超声是肿瘤定位的有效手段.监测肿瘤切除后血糖变化,结合术中快速病理可判定肿瘤是否完全切除.     

地氟醚与七氟醚对颅脑肿瘤手术患者血糖和乳酸的影响

目的研究地氟醚与七氟醚对颅脑肿瘤手术患者血糖和乳酸的影响。方法选择择期行颅脑肿瘤切除的患者64例,年龄21～62岁,ASA分级Ⅰ～Ⅱ级,体质指数20～25 kg/m2,采用随机数字表法分为地氟醚组(Group Des,n=30)与七氟醚组(Group Sevo,n=34),分别采用地氟醚、七氟醚吸入麻醉。分别于手术前(T0)、手术1小时(T1)、手术2小时(T2)、手术结束(T3)取动脉血1 m L,检测血糖和乳酸水平。结果两组患者血糖均升高,在四个不同时间点的比较差异有统计学意义(P0.01);各组在各时间点的比较无统计学意义(P0.05)。两组患者乳酸无明显升高,在各时间点的比较无统计学意义(P0.05);各组在各时间点的比较无统计学意义(P0.05)。结论地氟醚与七氟醚麻醉均增加颅脑肿瘤患者血糖水平。     

Transient hyperglycemia following intra-peritoneal irrigation with 5% glucose in a patient with pseudomyxoma peritonei

Pseudomyxoma peritonei is a condition characterized by the production of a large amount of mucopolysaccharide by a neoplastic epithelium. Although surgical removal of the mucinous ascites may be attempted, complete removal of the material is difficult. Thus, intra-peritoneal lavage with the liquid containing glucose or dextrose has been advocated to prevent reaccumulation of the mucus and complications such as bowel obstruction requiring repeated surgery. We report a case showing transient hyperglycemia following intra-peritoneal irrigation with 5% glucose in a patient with psudomyxoma peritonei. The patient was a 72-year-old woman. Preoperatively, she had hypertension and angina pectoris; but no history of glucose intolerance. Serum glucose was 92 mg x dl(-1). General anesthesia was induced with propofol (100 mg), vecuronium (6 mg), and fentanyl, and maintained with oxygen (33%), nitrous oxide and sevoflurane (1-2%). A mucinous tumor was found with a great deal of mucinous ascites. To remove the mucus and prevent subsequent re-accumulation, intra-peritoneal irrigation with 5% glucose in water was performed. Shortly after this procedure, the patient was found to be hyperglycemic (serum glucose 266 mg x dl(-1)) with normal oxygenation and hemodynamic data. The patient recovered uneventfully and could be extubated soon after surgery. Serum glucose level returned to 154 mg x dl(-1) one hour after surgery. Therefore, we think that this acute hyperglycemic condition, presumable due to intra-peritoneal irrigation, was transient. It is important to be aware of this dangerous complication associated with intra-peritoneal glucose instillation. Glucose monitoring during and after irrigation with glucose or dextrose is recommended.     

Reduction of glycemic potentiation. Sensitive indicator of beta-cell loss in partially pancreatectomized dogs

To determine which test of islet function is the most sensitive indicator of subclinical beta-cell loss, we studied six conscious dogs before and 1 and 6 wk after removal of the splenic and uncinate lobes [64 +/- 2% pancreatectomy (PX)]. To assess hyperglycemic potentiation, acute insulin secretory responses (AIR) to 5 g i.v. arginine were measured at the fasting plasma glucose (FPG) level after PG was clamped at approximately 250 mg/dl and after PG was clamped at a maximally potentiating level of 550-650 mg/dl. FPG levels were unaffected by PX (112 +/- 4 mg/dl pre-PX vs. 115 +/- 5 mg/dl 6 wk after PX, P NS). Similarly, basal insulin levels remained constant after PX (11 +/- 2 microU/ml pre-PX vs. 11 +/- 1 microU/ml 6 wk after PX, P NS). The AIR to 300 mg/kg i.v. glucose decreased slightly from 42 +/- 9 microU/ml pre-PX to 32 +/- 5 microU/ml 6 wk after PX (P NS), and thus the beta-cell loss was underestimated. In contrast, insulin responses to arginine declined markedly after PX. The AIR to arginine obtained at FPG levels declined from 23 +/- 3 microU/ml pre-PX to 13 +/- 2 microU/ml 6 wk after PX (P = .04). The AIR to arginine obtained at PG levels of approximately 250 mg/dl declined even more, from a pre-PX value of 56 +/- 7 microU/ml to 21 +/- 4 microU/ml 6 wk after PX (P = .02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Recently experienced ten cases of insulinoma--preoperative diagnosis of localization and intraoperative simultaneous monitoring of glucose and insulin

We have experienced 10 cases of insulinoma during the last 10 years from 1977 to 1986. All cases had strong hypoglycemic symptoms such as disturbance of consciousness, and insulinoma still tended to be misdiagnosed as epilepsy. The diagnosis of insulinoma was easily available from serum IRI (immunoreactive insulin)/plasma glucose ratio in all of the ten cases. As preoperative procedures for the diagnosis of localization, arteriography, computed tomography and portal blood sampling were positive in 6 of 8, 4 of 6 and 2 of 2 patients, respectively. At operation, all insulinomas could be identified by digital palpation. We performed simple excision of the tumor in 6 patients and distal pancreatectomy in 4 patients. The tumors were solitary and benign in all patients, ranging in size from 1.0 cm to 4.5 cm. Three cases were presented as case reports. In these cases, portal blood sampling and/or intraoperative monitoring of plasma glucose and serum IRI were performed. Portal blood sampling was effective even for a case which was negative in image diagnostic procedures. Furthermore, simultaneous monitoring of plasma glucose and serum IRI by quick radioimmunoassay seemed to be a good guide to the completeness of resection of insulin producing tumors.