Anaesthesia, 1977, Volume 32, pages 261-264 CASE REPORT
Anaesthetic management of insulinoma
P R A M I L A C H A R I , S. K. P A N D I T , R . N . K A T A R I A , H A R I W I R S I N G H , D. K . B A H E T I A N D J Y O T S N A W I G
Insulinoma is a rare tumour of the islet cells of the pancreas and was first described by Harris' in 1924. It can be benign or malignant. The clinical picture is due to periodic hypoglycaemia induced by increased secretion of insulin by the tumour. The symptoms may be suggestive of over-activity of the autonomic nervous system and may include hunger, tremors, sweating, tachycardia or disturbances of the central nervous system in the form of convulsions, unconciousness and changes in behaviour. Patients usually present themselves either to a neurologist or to a psychiatrist. The elective treatment of hyperinsulinism is surgical enucleation of adenoma or subtotal or total pancreatectomy. The results of surgery in cases which are not malignant are promising.2 The onset of the hypoglycaemic attacks can be very sudden and severe and may lead to permanent damage to the central nervous system and, consequently the anaesthetic management is considered hazardous unless strict precautions are taken. Four cases have been reported previously in the literat~re.j-~Two cases of insulinoma successfully treated surgically are presented in this paper. Case histories Case I A 45-year-old, very obese female weighing 90 kg
was admitted to the neurological service of our hospital with history of change in behaviour pattern for the last 5 years. She had been getting attacks of confusion, convulsions and coma. The frequency of such attacks had been increasing gradually and she was getting several attacks a day 15 days before surgery. The last attack before admission had been particularly severe and prolonged and had resulted in some degree of brain damage. A chance finding of a low blood sugar level raised the suspicion of insulinoma which was later confirmed by a tolbutamide tolerance test, a glucagon infusion test, a Hermen infusion test and extended glucose tolerance test. A single determination of fasting blood insulin level by the method of radio-immunoassay demonstrated the extremely high level of 180 pulml (normal 5 to 20 pulml).
Case 2
A 33-year-old male weighing 70 kg was admitted to the neurological service. His history was similar to Case 1 except that he had not sustained any brain damage. The same investigations were undertaken as for Case 1 and the diagnosis of insulinoma was confirmed. The fasting blood insulin level was 150 pulml.
Pramila Chari, MD, Lecturer in Anaesthesia, S. K. Pandit, MS, PhD, FFARCS, Associate Professor of Anaesthesia, R. N. Kataria, FRCS, Assistant Professor of Surgery, Harivir Singh, MS, DA, Associate Professor of Anaesthesia, D. K. Baheti, MD, Registrar in Anaesthesia and Jyotsna Wig, MD, Registrar in Anaesthesia, Department of Anaesthesiology and Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Dr S. K. Pandit is at present at the University of Colorado. Address for correspondence: Dr Pramila Chari, Department of Anaesthesiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
261
262
P. Chart et al.
In both cases the symptoms of hypoglycaemia were controlled with 50gof glucose administered every 2 hours by mouth. Both patients were eventually explored for insulin producing tumour. Anaesthetic management
Both patients were sedated with oral diazepam, 10 mg, given every 6 hours, starting 18 hours before surgery. Two hourly intragastric feeding of 50 g of glucose was continued as before and the last intragastric feed was given 5 hours before surgery and 1 hour later, 4 hours before surgery, intravenous infusion with 10% dextrose was started and continued at the rate of 50 g every 2 hours. Blood glucose estimations 2 hours before the start of surgery were 200 mg% in Case 1 and 117 mg% in Case 2. An hour before surgery the patient was premedicated with 75 mg of pethidine and 10 mg of diazepam intramuscularly. A central venous line was established on arrival in the theatre suite reaching the superior vena cava for infusion of hypertonic glucose solutions and for the monitoring of central venous pressure. Induction was carried out with thiopentone, followed by suxamethoniumto facilitate tracheal intubation. Anaesthesia was maintained with 5 litres of
nitrous oxide and 3 litres of oxygen with intermittent methoxyflurane (0.25-0.5%). Muscle relaxation was obtained with pancuronium bromide and respiration was controlled with the help of a Manley ventilator. The blood pressure, pulse, central venous pressure (Fig. l), urinary output (Table l), the blood sugar (Fig. 2)-using
8oot 700
i\ -4
I
Operative
- - _ ,_Case 1 :-,
B.P.mmHg Pulse/mi n
Case 2.
Table 1. Fluid intake and output during anaesthesia Fluids
B.P. mmHg
Post operative
Fig. 2. Blood sugar levels during and after surgery
Blood 10% dextrose 25% dextrose Normal saline Urinary output
Case1
Case2
350* 350
700 650 lo00 1200 2250
700 lo00 1200
Pulse/min
0
20 40 60 80 100 120 140 160 180 200 Time
Fig. 1. Systolic blood pressure; pulse; central venous pressure monitoring during surgery. - - - -, Case 1 ;
-,Case 2.
on the spot 'dextrostick' and detailed laboratory methods-and the electrocardiograph (ECG) were monitored during surgery. In order to meet the body glucose requirement and also to avoid excessive infusion, 25% dextrose was infused, but both the cases showed signs of hypoglycaemia as evidencedby profuse sweating, bradycardia and hypotension during the manipulation of the tumour by the surgeon.
Anaesthetic management of insulinoma At this time blood sugar level as estimated by 'Dextrostick' was found to be below 90 mg% in both patients and this was treated by rapid infusion of dextrose. Blood loss was adequately replaced in both cases. Tumours were found in the tail of the pancreas in Case 1 and in the body of the pancreas in Case 2. Distal pancreatectomy along with splenectomy was undertaken in both cases. Glucose infusion was replaced by normal saline after removal of the tumour. There was no further episode of hypoglycaemia during the rest of the operation. At the end of surgery the residual effect of the pancuronium bromide was reversed with neostigmine bromide 2.5 mg and atropine sulphate 1.2 mg. In the recovery room both the patients were fully concious with stable cardiovascular and respiratory systems. Blood sugar level at the end of surgery was higher than normal but gradually came down to near normal level during the course of next 3 days. The postoperative period was uneventful. The course of anaesthesia, blood sugar levels and blood insulin levels during surgery and in the immediate postoperative period are shown in Figs 1-3. Serum insulin levelpu/ml
Handling of tumour
Removal of turnour
-1
Completion of operation
Post op.doy
Fig. 3. Serum insulin levels during surgery and o n the
first postoperative day. - - - -, Case 1 ; -,
Case 2.
263
The duration of anaesthesia was 2 hours in Case 1 and 30 minutes in Case 2. The amounts of fluids infused and urinary output during this period are shown in Table 1. Histological examination disclosed an islet cell adenoma with hyperplasia of surrounding islet tissue in Case 1 and a simple adenoma with scanty islet tissue in Case 2.
Discussion The maintenance of adequate blood sugar levels during the pre-operative and operative periods is of primary importance in the anaesthetic management of insulinomas. These patients can go into hypoglycaemic attacks during operation if glucose is withheld over a long period of time or the patients are kept fasting for a long period, as was shown by the case reports of Fraser2 and of Hargadon & Ormston. The glucose intake of the cases presented here was maintained at regular intervals through intragastric feeds during the night until 5 hours before the induction of anaesthesia. One hour after the last intragastric feed a n intravenous infusion of dextrose was started. In spite of this the initial handling of the tumour in both the patients caused transient attacks of profuse sweating, hypotension and bradycardia, presumably due to hypoglycaemia. A rapid infusion of hypertonic (25%) dextrose promptly stabilised the condition of the patients. Bradycardia is not a usual feature of hypoglycaemia but this may have been the result of vagal stimulation caused by hypoglycaemia. Steroid therapy before and during operation has been advocated, but its value is doubtful and it may even be harmful. Corticosteroid therapy has several disadvantages including exaggeration of the normal hyperglycaemic response in the postoperative period with simultaneous interference with the utilisation of glucose at the tissue leveL6 Hargadon & Ormston3 suggested that only nitrous oxide and oxygen should be used for induction and maintenance of anaesthesia, since all other anaesthetics produce hyperglycaemia. They condemned halothane because of its hypotensive effect. Bourke4 also suggested that halothane should be avoided because it causes increased sensitivity to insulin. Intermittent methoxyflurane was used in our cases because of its known hyperglycaemic effect. This might help
264
P. Chari et al.
to maintain the blood sugar at higher level in the early part of the operation. Nitrous oxide and oxygen alone give a very light plane of anaesthesia which might lead to movement o r awareness. Pancuronium bromide was used because it is known to provide a stable cardiovascular condition as compared with tubocurarine.’ It took 3-4 days for the blood sugar level to come to within normal limits and similar experiences have also been encountered by other authors3v4 This is to be expected, because the anti-insulin hormones like glucagon, growth hormones and glucocorticoids, persist at higher levels for a few days even after removal of the tumour. Insulin therapy is, however, rarely indicated as this hyperglycaemia is self limiting. Summary
The anaesthetic management of two cases of insulinoma treated by distal pancreatectomy is presented. Stress is laid on pre-operative and intra-operative glucose administration in sufficiently high quantity. Pre-operative corticosteroid therapy is better avoided. Dextrose infusion should be stopped soon after removal of the tumour to prevent excessive hyperglycemic response in the postoperative period. Methoxyflurane was used because it tends to raise the blood sugar level. Pancuronium bro-
mide was preferred because of the stable cardiovascular conditions it produces. Key words ANAESTHESIA; insulinoma. METABOLISM; hyperinsulinism.
1.
2. 3. 4. 5.
6.
I.
References HARRIS, S. (1924) Hyperinsulinism and dysinsulinism. Journal of the American Medical Association, 83, 729. (Quoted by MARKS, V. & ROSE,F.C. (1965) Hypoglycaemia, p. 104. Blackwell Scientific Publications, Oxford.) FRASER, R.A. (1963) Hyperinsulinism under anaesthesia in a case of islet cell tumour of the pancreas. Anaesthesia, 18, 3. HAROADON, J.J. & ORMSTON, T.O.G. (1963) Anaesthesia for excision of islet-cell turnour of the pancreas : case report. British Journal of Anaesthesia, 35, 807. BOURKE,A.M. (1966) Anaesthesia for the surgical treatment of hyperinsulinism: case report. Anaesthesia, 21, 239. T~RNBLOM, N. (1961) Hyperinsulinisrn with fatal postoperative hyperthermia. Acta Medica Scandinaoica, 110. 757. ADEZATI, L. (1964) Adrenal steroids and adipose tissue. In: Hormonal steroids: biochemistry, pharmacology and therapeutics: Proceedings of the first International congress on hormonal steroids, Milan (Ed. by L. Martini & A. Pecile) Vol. I, p. 317. Academic Press, London. PANDIT, S.K., DUNDEE, J.W. & STEVENSON, H.M. (1961) A clinical comparison of pancuronium with tubocurarine and alcuronium in major cardiothoracic surgery. Anesthesia and Analgesia: Current Researches, 50, 926.
Anaesthetic management of insulinoma
P R A M I L A C H A R I , S. K. P A N D I T , R . N . K A T A R I A , H A R I W I R S I N G H , D. K . B A H E T I A N D J Y O T S N A W I G
Insulinoma is a rare tumour of the islet cells of the pancreas and was first described by Harris' in 1924. It can be benign or malignant. The clinical picture is due to periodic hypoglycaemia induced by increased secretion of insulin by the tumour. The symptoms may be suggestive of over-activity of the autonomic nervous system and may include hunger, tremors, sweating, tachycardia or disturbances of the central nervous system in the form of convulsions, unconciousness and changes in behaviour. Patients usually present themselves either to a neurologist or to a psychiatrist. The elective treatment of hyperinsulinism is surgical enucleation of adenoma or subtotal or total pancreatectomy. The results of surgery in cases which are not malignant are promising.2 The onset of the hypoglycaemic attacks can be very sudden and severe and may lead to permanent damage to the central nervous system and, consequently the anaesthetic management is considered hazardous unless strict precautions are taken. Four cases have been reported previously in the literat~re.j-~Two cases of insulinoma successfully treated surgically are presented in this paper. Case histories Case I A 45-year-old, very obese female weighing 90 kg
was admitted to the neurological service of our hospital with history of change in behaviour pattern for the last 5 years. She had been getting attacks of confusion, convulsions and coma. The frequency of such attacks had been increasing gradually and she was getting several attacks a day 15 days before surgery. The last attack before admission had been particularly severe and prolonged and had resulted in some degree of brain damage. A chance finding of a low blood sugar level raised the suspicion of insulinoma which was later confirmed by a tolbutamide tolerance test, a glucagon infusion test, a Hermen infusion test and extended glucose tolerance test. A single determination of fasting blood insulin level by the method of radio-immunoassay demonstrated the extremely high level of 180 pulml (normal 5 to 20 pulml).
Case 2
A 33-year-old male weighing 70 kg was admitted to the neurological service. His history was similar to Case 1 except that he had not sustained any brain damage. The same investigations were undertaken as for Case 1 and the diagnosis of insulinoma was confirmed. The fasting blood insulin level was 150 pulml.
Pramila Chari, MD, Lecturer in Anaesthesia, S. K. Pandit, MS, PhD, FFARCS, Associate Professor of Anaesthesia, R. N. Kataria, FRCS, Assistant Professor of Surgery, Harivir Singh, MS, DA, Associate Professor of Anaesthesia, D. K. Baheti, MD, Registrar in Anaesthesia and Jyotsna Wig, MD, Registrar in Anaesthesia, Department of Anaesthesiology and Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Dr S. K. Pandit is at present at the University of Colorado. Address for correspondence: Dr Pramila Chari, Department of Anaesthesiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
261
262
P. Chart et al.
In both cases the symptoms of hypoglycaemia were controlled with 50gof glucose administered every 2 hours by mouth. Both patients were eventually explored for insulin producing tumour. Anaesthetic management
Both patients were sedated with oral diazepam, 10 mg, given every 6 hours, starting 18 hours before surgery. Two hourly intragastric feeding of 50 g of glucose was continued as before and the last intragastric feed was given 5 hours before surgery and 1 hour later, 4 hours before surgery, intravenous infusion with 10% dextrose was started and continued at the rate of 50 g every 2 hours. Blood glucose estimations 2 hours before the start of surgery were 200 mg% in Case 1 and 117 mg% in Case 2. An hour before surgery the patient was premedicated with 75 mg of pethidine and 10 mg of diazepam intramuscularly. A central venous line was established on arrival in the theatre suite reaching the superior vena cava for infusion of hypertonic glucose solutions and for the monitoring of central venous pressure. Induction was carried out with thiopentone, followed by suxamethoniumto facilitate tracheal intubation. Anaesthesia was maintained with 5 litres of
nitrous oxide and 3 litres of oxygen with intermittent methoxyflurane (0.25-0.5%). Muscle relaxation was obtained with pancuronium bromide and respiration was controlled with the help of a Manley ventilator. The blood pressure, pulse, central venous pressure (Fig. l), urinary output (Table l), the blood sugar (Fig. 2)-using
8oot 700
i\ -4
I
Operative
- - _ ,_Case 1 :-,
B.P.mmHg Pulse/mi n
Case 2.
Table 1. Fluid intake and output during anaesthesia Fluids
B.P. mmHg
Post operative
Fig. 2. Blood sugar levels during and after surgery
Blood 10% dextrose 25% dextrose Normal saline Urinary output
Case1
Case2
350* 350
700 650 lo00 1200 2250
700 lo00 1200
Pulse/min
0
20 40 60 80 100 120 140 160 180 200 Time
Fig. 1. Systolic blood pressure; pulse; central venous pressure monitoring during surgery. - - - -, Case 1 ;
-,Case 2.
on the spot 'dextrostick' and detailed laboratory methods-and the electrocardiograph (ECG) were monitored during surgery. In order to meet the body glucose requirement and also to avoid excessive infusion, 25% dextrose was infused, but both the cases showed signs of hypoglycaemia as evidencedby profuse sweating, bradycardia and hypotension during the manipulation of the tumour by the surgeon.
Anaesthetic management of insulinoma At this time blood sugar level as estimated by 'Dextrostick' was found to be below 90 mg% in both patients and this was treated by rapid infusion of dextrose. Blood loss was adequately replaced in both cases. Tumours were found in the tail of the pancreas in Case 1 and in the body of the pancreas in Case 2. Distal pancreatectomy along with splenectomy was undertaken in both cases. Glucose infusion was replaced by normal saline after removal of the tumour. There was no further episode of hypoglycaemia during the rest of the operation. At the end of surgery the residual effect of the pancuronium bromide was reversed with neostigmine bromide 2.5 mg and atropine sulphate 1.2 mg. In the recovery room both the patients were fully concious with stable cardiovascular and respiratory systems. Blood sugar level at the end of surgery was higher than normal but gradually came down to near normal level during the course of next 3 days. The postoperative period was uneventful. The course of anaesthesia, blood sugar levels and blood insulin levels during surgery and in the immediate postoperative period are shown in Figs 1-3. Serum insulin levelpu/ml
Handling of tumour
Removal of turnour
-1
Completion of operation
Post op.doy
Fig. 3. Serum insulin levels during surgery and o n the
first postoperative day. - - - -, Case 1 ; -,
Case 2.
263
The duration of anaesthesia was 2 hours in Case 1 and 30 minutes in Case 2. The amounts of fluids infused and urinary output during this period are shown in Table 1. Histological examination disclosed an islet cell adenoma with hyperplasia of surrounding islet tissue in Case 1 and a simple adenoma with scanty islet tissue in Case 2.
Discussion The maintenance of adequate blood sugar levels during the pre-operative and operative periods is of primary importance in the anaesthetic management of insulinomas. These patients can go into hypoglycaemic attacks during operation if glucose is withheld over a long period of time or the patients are kept fasting for a long period, as was shown by the case reports of Fraser2 and of Hargadon & Ormston. The glucose intake of the cases presented here was maintained at regular intervals through intragastric feeds during the night until 5 hours before the induction of anaesthesia. One hour after the last intragastric feed a n intravenous infusion of dextrose was started. In spite of this the initial handling of the tumour in both the patients caused transient attacks of profuse sweating, hypotension and bradycardia, presumably due to hypoglycaemia. A rapid infusion of hypertonic (25%) dextrose promptly stabilised the condition of the patients. Bradycardia is not a usual feature of hypoglycaemia but this may have been the result of vagal stimulation caused by hypoglycaemia. Steroid therapy before and during operation has been advocated, but its value is doubtful and it may even be harmful. Corticosteroid therapy has several disadvantages including exaggeration of the normal hyperglycaemic response in the postoperative period with simultaneous interference with the utilisation of glucose at the tissue leveL6 Hargadon & Ormston3 suggested that only nitrous oxide and oxygen should be used for induction and maintenance of anaesthesia, since all other anaesthetics produce hyperglycaemia. They condemned halothane because of its hypotensive effect. Bourke4 also suggested that halothane should be avoided because it causes increased sensitivity to insulin. Intermittent methoxyflurane was used in our cases because of its known hyperglycaemic effect. This might help
264
P. Chari et al.
to maintain the blood sugar at higher level in the early part of the operation. Nitrous oxide and oxygen alone give a very light plane of anaesthesia which might lead to movement o r awareness. Pancuronium bromide was used because it is known to provide a stable cardiovascular condition as compared with tubocurarine.’ It took 3-4 days for the blood sugar level to come to within normal limits and similar experiences have also been encountered by other authors3v4 This is to be expected, because the anti-insulin hormones like glucagon, growth hormones and glucocorticoids, persist at higher levels for a few days even after removal of the tumour. Insulin therapy is, however, rarely indicated as this hyperglycaemia is self limiting. Summary
The anaesthetic management of two cases of insulinoma treated by distal pancreatectomy is presented. Stress is laid on pre-operative and intra-operative glucose administration in sufficiently high quantity. Pre-operative corticosteroid therapy is better avoided. Dextrose infusion should be stopped soon after removal of the tumour to prevent excessive hyperglycemic response in the postoperative period. Methoxyflurane was used because it tends to raise the blood sugar level. Pancuronium bro-
mide was preferred because of the stable cardiovascular conditions it produces. Key words ANAESTHESIA; insulinoma. METABOLISM; hyperinsulinism.
1.
2. 3. 4. 5.
6.
I.
References HARRIS, S. (1924) Hyperinsulinism and dysinsulinism. Journal of the American Medical Association, 83, 729. (Quoted by MARKS, V. & ROSE,F.C. (1965) Hypoglycaemia, p. 104. Blackwell Scientific Publications, Oxford.) FRASER, R.A. (1963) Hyperinsulinism under anaesthesia in a case of islet cell tumour of the pancreas. Anaesthesia, 18, 3. HAROADON, J.J. & ORMSTON, T.O.G. (1963) Anaesthesia for excision of islet-cell turnour of the pancreas : case report. British Journal of Anaesthesia, 35, 807. BOURKE,A.M. (1966) Anaesthesia for the surgical treatment of hyperinsulinism: case report. Anaesthesia, 21, 239. T~RNBLOM, N. (1961) Hyperinsulinisrn with fatal postoperative hyperthermia. Acta Medica Scandinaoica, 110. 757. ADEZATI, L. (1964) Adrenal steroids and adipose tissue. In: Hormonal steroids: biochemistry, pharmacology and therapeutics: Proceedings of the first International congress on hormonal steroids, Milan (Ed. by L. Martini & A. Pecile) Vol. I, p. 317. Academic Press, London. PANDIT, S.K., DUNDEE, J.W. & STEVENSON, H.M. (1961) A clinical comparison of pancuronium with tubocurarine and alcuronium in major cardiothoracic surgery. Anesthesia and Analgesia: Current Researches, 50, 926.
