BY D. W. J. CULLINGFORD Anaesthetic Departments, East Birmingham Hospital and Dudley Road Hospital, Birmingham, England SUMMARY

Transcription

1 Brit. J. Anaesth. (966), 38, 463 THE BLOOD SUGAR RESPONSE TO ANAESTHESIA AND SURGERY IN SOUTHERN INDIANS A comparison between South Indian and European patients in the Christian Medical College and Hospital, Vellore, South India BY D. W. J. CULLINGFORD Anaesthetic Departments, East Birmingham Hospital and Dudley Road Hospital, Birmingham, England SUMMARY During the course anaesthesia and surgery in South India, it was noticed that Indian and European patients responded differently. In an attempt to evaluate these differences, values were used as a guide to the sympathetic nervous response. Under general anaesthesia values rose and stayed higher in Indian patients than in Europeans in India or England. General anaesthesia by itself provoked no elevation until the commencement surgical trauma. Under subarachnoid or epidural analgesia, no major change in occurred during surgery. During the study involving 4 patients, three collapsed unexpectedly and resuscitative measures invalidated the results. Although nutrition might play some part, the differences are considered to be racial and not climatic. The operative risk amongst the Negro population the United States is recognized to be greater than that Europeans. Gregory (949) stated that even apparently fit Negroes were liable to sudden death under anaesthesia. Veal and van Werden (936) reported 30 deaths, which 2 were in Negroes, and Trent and Gaster (944) found that in a group containing per cent Negroes and 8 per cent Europeans, 66 per cent all the operating room deaths occurred in the Negro group. Keating (9) drew attention to the problems facing anaesthetists in tropical countries, and gave examples the excessive autonomic reaction to surgical procedures Jamaicans as compared to Europeans. At the Christian Medical College and Hospital at Vellore in South India the author observed differences in the response Indian and British patients undergoing surgery. On occasions Indian patients collapsed suddenly on the operating table. Whilst some these episodes may have been due to an unusual reaction to drugs (Cullingford, 963), others developed a severe degree hypotension with peripheral vascular failure for no apparent reason. Studies values during anaesthesia and surgery were conducted because several authors have suggested that the response hyperglycaemia as a result catecholamine release is an effective, if crude, indicator the stress response (Keating, 98; Annamunthodo, Keating and Patrick, 98). There are differences between people from the various parts India, but the patients studied came from the immediate locality Vellore and can be regarded as a typical sample South Indians. METHOD Before induction anaesthesia, and then at half-hourly intervals, a sample venous blood was taken. In order to obviate errors blood was first aspirated and the syringe rinsed with this sample which was then discarded. The syringe was filled with a second sample blood and this was then placed in a container with potassium oxalate and sodium fluoride. The content was estimated by the method Folin- Wu, as modified by Haslewood and Strookman (939) (quoted Varley, 962). This estimates any reducing sugar present, including glucose. Galac-

2 464 BRITISH JOURNAL OF ANAESTHESIA tose is the only other likely reducing agent and the values are interpreted as being glucose alone. Material. Blood sugar estimations were carried out during various operations, but for clarity the results relating only to those Indians undergoing laparotomy and herniorrhaphy under general anaesthesia, and Indians undergoing operations under spinal and epidural analgesia, are reported here. Five Europeans at Vellore were also studied. Comparison is made with British figures. On the occasions when the start the operation was delayed by 30 minutes the opportunity was taken to determine the response the to anaesthesia without surgery. Estimations were terminated when a blood transfusion was started since the sugar in the stored blood upset the readings. 22O -i Anaesthesia. Pre-operative medication was with pentobarbitone 0-0 mg and hyoscine 0.2 mg together with morphine 0 mg or pethidine 0-00 mg. The exact dosage each drug depended upon the patient's body weight. In some patients general anaesthesia was induced with nitrous oxide, while in others a sleep dose 2. per cent thiopentone was given. About 00 mg thiopentone sufficed for most Indians, whereas the Europeans required far more than one would expect from their slightly greater body weight. Intubation was achieved with the aid suxamethonium or, occasionally, gallamine. The relaxant dosage was approximately the same for Indians and Europeans. General anaesthesia was maintained either with nitrous oxide, oxygen and pethidine or with nitrous oxide, oxygen and low concentrations ether. In both cases a circle absorber with INDIANS Time O \ in hours FIG. Percentage change in values on Southern Indian and European patients before and during general anaesthesia for surgery. Line Upper laparotomies on nine Southern Indians. 2 Vagotomy and gastrojejunostomy on ten Southern Indians. 3 Herniorrhaphy on five Southern Indians. 4 Five Europeans at Vellore. Fourteen thoracotomies in England. 6 Ten gastrectomies in England.

3 BLOOD SUGAR RESPONSE TO ANAESTHESIA AND SURGERY 46 a leak was employed. Gallamine was used to obtain abdominal relaxation when this was necessary. When spinal analgesia was employed this was induced with heavy cinchocaine. Epidural block was performed with.6 per cent lignocaine containing in 200,000 adrenaline. All patients undergoing laparotomy received a saline drip infusion. RESULTS The changes during various operations are given in figures -3. For ease comparison in these figures, relative values are shown rather than absolute values. These relative values are the levels expressed as the mean the percentage each pre-induction value. The tables show the range and mean the absolute values as well as the calculated percentage. During nine upper abdominal operations under general anaesthesia in Indians (table I, fig., line ), the rose steadily to a maximum at about 2 hours. In ten Indians who underwent vagotomy and gastroenterostomy (table II; fig., 22O-, TABLE I Upper laparotomies under general anaesthesia (excluding gastrojejunostomies in table II) m Southern Indians Time (hr) No. cases Range < TABLE II Gastrojejunostomy and vagotomy under general anaesthesia in Southern Indians Time (hr) 0 No. cases 0 8 Range OOo o I6O - o.c o I4O- 8O O _L 2 I Time in hours FIG. 2 Percentage change in values on Southern Indian patients during operation under spinal and epidural analgesia. Dotted line Twenty-two Southern Indians under epidural analgesia. Solid line Eight Southern Indians under spinal analgesia.

4 466 BRITISH JOURNAL OF ANAESTHESIA 22O-n 8O Time 2 In hours FIG. 3 Percentage change in values Southern Indian patients during general anaesthesia. Surgery was delayed half-hour after induction anaesthesia, during which time no rise in occurred, despite the use ether. Line Nitrous oxide, oxygen, pethidine, and relaxant. Five Southern Indians. 2 Nitrous oxide, oxygen, light ether, and relaxant. Eleven Southern Indians. line 2) the values tended to level out after hour, by which time the vagotomy would have severed the visceral afferent impulses. A similar rise was also observed in five patients who underwent herniorrhaphy (table III; fig., line 3). Blood sugar changes in five acclimatized Europeans also rose during general anaesthesia (table IV; fig., line 4), but the rise was much less marked than in the Indians, and similar to that a group patients anaesthetized by the author for major thoracic operations in England (table V; fig., line ), the values for which were estimated by the glucose oxidase method. In all these operations an identical anaesthetic technique was maintained as far as possible, although in the English cases in table V tie pre-anaesthetic medication was less soporific than the Indian cases, papaveretum 20 mg and hyoscine 0.4 mg being used without a barbiturate. In the thoracic opera- TABLE III Herniorrhaphy under general anaesthesia in Southern Indians Time (hi) No. cases Range i li tions haemorrhage on occasions was considerably greater than in those the Indians under comparison. Blood loss alone might result in elevation values, but Lawrence and Plaut (942) found that the controlled haemorrhage in blood donors did not produce a statistically significant effect in this respect.

5 BLOOD SUGAR RESPONSE TO ANAESTHESIA AND SURGERY 467 TABLE IV Blood sugar values on European patients undergoing operation at Vellore under general anaesthesia. Time (hr) 0 No. cases 4 4 Range TABLE VII Blood sugar values during subarachnoid analgesia in Southern Indians Time (hr) No. cases Range 0 8 i li TABLE V Blood sugar during thoracotomy on English patients in England. Time (hr) 0 li No. cases Range mg/00 ml) TABLE VI English values s for gastrectomy in England for comparison (jrom Griffiths (93) by kind permission the author and the Editor Quart. J. Med.) Time (min) No. cases Percentage Griffiths' (93) figures for English patients anaesthetized with nitrous oxide, oxygen and pethidine are reproduced in table VI (fig., line 6). He estimated by the method Fugita and Iwatake, and found even less change in during gastrectomy. Presumably blood loss in his series would be similar to that the Indians. Thirty patients underwent operations under spinal and epidural analgesia (tables VII and VHI; fig. 2) and sustained no statistically significant change in throughout the entire procedure. Greene's observations on Western subjects (98) thus applies also to Indian patients. The spinal and epidural groups did not differ significantly from each other. TABLE VIII Blood sugar during epidural analgesia in Southern Indians. Time (hr) 0 i li 2 No. cases Range TABLE IX The effect anaesthesia with nitrous oxide and pethidine on the Southern Indians. The start surgery is one half hour after induction. Time (hr) 0 li No. cases Range The use pethidine (table IX; fig. 3, line ) instead ether (table X; fig. 3, line 2) as a supplement to nitrous oxide and oxygen did not prevent the rise in with surgery. In the absence surgical trauma, where the start the operation was delayed for half an hour, the remained substantially unchanged with either adjuvant. Contrary to expectations, the did not rise with the use ether until the onset surgical stimuli. Blood sugar changes wete also followed in three patients undergoing neurosurgery under hypothermia; in all there was a considerable rise (table XI).

6 468 BRITISH JOURNAL OF ANAESTHESIA Table XII(A) is a statistical comparison at and H hours between the percentage values for the nineteen Indians in India in tables I and II with the nineteen Europeans in India and England in tables IV and V. These groups were all anaesthetized by the author to minimize any personal error. Table XII(B) compares statistically at and 2 hours the percentage values for the nineteen Indians in India with ten British patients undergoing similar surgery in England. TABLE X The effect ether on Southern Indians. During the half-hour prior to the start surgery there is no rise. Time (hr) No. cases Range i H In each instance, the mean difference is three to four times the standard error the mean and therefore highly significant. Three Indian patients under general anaesthesia in the total series 4 patients collapsed suddenly and unexpectedly shortly after the start surgery. Concentration upon resuscitation, combined with the difficulty in obtaining adequate samples fresh blood from collapsed veins resulted in few readings being obtained, which were doubtful accuracy. These showed no elevation the until the blood pressure and peripheral vascular state had returned to normal, when the rose. Some this rise might be caused by the administration a vasopressor or the infusion stored blood containing glucose, Because the possible errors, these patients are omitted from the tables. It is interest that one these patients had collapsed in a similar way on a previous occasion, when the laparotomy which was being undertaken was abandoned, although subsequently he behaved normally during a third anaesthetic for the opening a colostomy. TABLE XI The response to hypothermia for neurosurgery in three Southern Indian patients. Figures in parentheses indicate percentage. Time (hr) 0 H Blood sugar (mg/00 Patient (a) Patient (b) Patient (c) ml) 6 at 36"C (00) 67at36 C (00) at36.3*c (00) 0at34. C (3) 7at36 C () 79at33. C (8) 0 at 32 C (7) 70 at 33. (48) c 28at32*C (97) 2at32'C (324) TABLE XII Statistical comparison. (A) Comparing the relative percentage values the value the Indians in tables I and II with the Europeans m tables IV and V. At At hour H[ hours (B) Comparing the relative percentage values the bloodsugar theindians m tables I and II with Griffiths' patients in lauie i VI. At At 2 nours hour Tables l&ii Tables I & II Tables IV &V Table VI difference difference Standard error Standard error t t P <0.00 <0.00 P <0.0 <0.0

7 BLOOD SUGAR RESPONSE TO ANAESTHESIA AND SURGERY 469 DISCUSSION These studies show that in Indian patients in Vellore undergoing similar forms surgery and comparable general anaesthesia a greater rise in content occurred than in European patients in either India or England. Nutritionally, the patients varied from gross emaciation to near obesity, which may be the cause the wide variation in fasting blood levels. If so, this bears out an observation by Ma (962) who found that the fasting blood levels in healthy Chinese in Hong Kong varied from 8 to 0 mg/00 ml in proportion to their social and economic status. One would have thought that malnutrition with a reduced liver glycogen might Limit glucogenesis and restrict the hyperglycaemia (Cantarow and Trumper, 962). Both laparotomies (table I) and gastrojejunostomies (table II) included emaciated patients and it is suggested that the slight difference between the two groups is caused by the vagotomy preceding the gastrojejunostomy. Exposure die abdominal vagus produces a fairly severe surgical stimulus at an early stage the operation, but once the nerve fibres are divided, the stimulus is reduced and the response curve tends to level out. This is substantiated by the evidence that a subarachnoid or epidural block completely eliminates the rise to all types surgery. These blocks, however, cut f both the afferent stimuli and the efferent impulses to the adrenal glands (White, Smithwick and Simeone, 92). Consideration must also be given to the possibility that the hyperglycaemia observed was due to the ether anaesthesia (Keeton and Ross, 99). With the concentrations ether used in this study, there was no rise in until surgery commenced, when the response from patients having nitrous oxide, oxygen and pethidine anaesthesia differed very little from those having nitrous oxide, oxygen and minimal ether (fig- 3). The possibility that morphine might be responsible for the hyperglycaemia requires consideration. Goodman and Gilman (9) state that this effect is inconstant, and is mediated through the adrenal medulla. In fact, the response was similar whatever the pre-operative medication. The Indian patients were better sedated on their arrival in the anaesthetic room than the average British patient so that any rise in content as a result anxiety should be minimized. In the same context it is significant that excitement during induction with nitrous oxide and oxygen was not encountered. Even allowing for weight and comparative pre-anaesthetic medication, the Indians tolerated only small doses thiopentone and pethidine, whereas they required similar doses relaxant to the Europeans. The difference may be racial or nutritional. Many South Indians have a darker skin than North Indians and the relationship between skin pigmentation and autonomic or suprarenal activity requires investigation, although Blane (99) could not confirm any connection between skin colour and steroid secretion. The collapse three patients (2 per cent) during a minor part an operative procedure is in conformity with the Negro risk, to which reference has already been made. In conclusion, if the rise in is a true indicator the sympathetic response during surgery, Indian patients in South India react more in this respect than Europeans under the same conditions either in a tropical or temperate climate. Although nutrition might play some part in this, the differences are not climatic but racial. ACKNOWLEDGEMENTS I wish to acknowledge gratefully the help given me by a number people at Vellore: Miss Nash and the staff the clinical biochemistry department for carrying out a large number estimations; Dr. Gwenda Lewis, Dr. George Varkey and the members the anaesthetic department for their co-operation, the surgeons for their tolerance, and the statisticians for help with the results. My thanks are also due to Pressor Mushin and other colleagues in this country who have given me assistance with the preparation this paper. The use tables from the Quarterly Journal Medicine (93) is acknowledged with thanks. REFERENCES Annamunthodo, H., Keating, V. J., and Patrick, S. J. (98). Liver glycogen alterations in anaesthesia and surgery. Anaesthesia, 3, 4, 429. Blane, G. F. (99). Urinary 7-ketosteroids and ketogenic steroids in a mixed Jamaican population. Lancet,, 498. Cantarow, A., and Trumper, M. (962). Clinical Biochemistry, 6th ed., p. 36. Philadelphia: Saunders. Cullingford, D. W. J. (963). Ergometrine and "syntometrine" in obstetrics. Brit med. J., 2, 386.

8 470 BRITISH JOURNAL OF ANAESTHESIA Goodman, L. S., and Gilman, A. (9). The Pharmacological Basis Therapeutics, 2nd ed., p New York: Macmillan. Greene, N. M. (98). Physiology Spinal Anesthesia, p. 6. Baltimore: Williams and Wilkins. Gregory, J. E. (949). The pathology sudden and unexpected death under anesthesia. Anesthesiology, 0, 0. Griffiths, J. A. (93). The effects general anaesthesia and hexamethonium on the in non-diabetic and diabetic surgical patients. Quart. J. Med., 22, 40. Lawrence, B. J., and Plaut, G. (942). The effect bleeding on the level in blood donors. Brit. med. J., 2, 8. Keating, V. J. (9). Anaesthetic problems in a tropical country. Proc. World Congress Anaesthesiologists, p Scheveningen, Holland. (98). Carbohydrate metabolism: The effects surgery in a tropical population. Anaesthesia, 3, 4, 434. Keeton, R. W., and Ross, E. L. (99). The mechanics ether hyperglycemia. Amer. J. Physiol., 48, 46. Ma, L. (962). A survey blood constituents healthy Chinese in Hong Kong. Trans, roy. Soc. trop. Med Hyg., S6, 3, 222. Trent, J. C, and Gaster, E. (944). Anesthetic deaths in 4,28 consecutive cases. Ann. Surg., 9, 94. Varley, H. (962). Practical Clinical Biochemistry. 3rd ed., p. 3. London: Heinemann. Veal, J. R., and van Werden, B. de K. (936). Mortality spinal analgesia. Amer. J. Surg., 34, 606. White, J. C, Smithwick, R. H., and Simeone, F. A. (92). The Autonomic Nervous System, 3rd ed., p. 49. New York: Macmillan. VARIATIONS DE LA GLYCEMIE PENDANT L'ANESTHESIE ET LES INTERVENTIONS CHIRURGICALES CHEZ DES INDIENS DU SUD SOMMAIRE On a constate dans le sud des Indes que les Indiens et les Europeens reagissaient diffirement a l'anesthesie et aux interventions chirurgicales. Pour essayer de preciser cette difference, on a mesuri la glycemie, dans l'idee qu'elle donnait un reflet des reactions du systeme nerveux sympathique. En anesthesie gdnirale, la glycemie augmente plus et reste a un niveau plus ilevi chez les Indiens que chez les Europeens, et c:la aussi bien aux Indes qu'en Angleterre. L'anesthesie genirale en elle meme ne provoque pas d'hyperglycemie avant que n'intervienne le traumatisme chirurgical. Si l'anesthesie se fait par voie sous-arachnoidienne ou 6pidurale, Foperation n'amene pas de variations notables de la glycemie. Trois des 4 patients Studies eurent un collapsus inattendu, mais le traitement de reanimation fit que Ton ne put tenir compte des glycemies mesurees chez eux. Le mode d'alimentation joue probablement un r6e dans les differences observees, mais on estime que celles-ci sont liees a la race et non au climat. DIE VERANDERUNG DES BLUTZUCKER- SPIEGELS DURCH DIE NARKOSE UND CHIRURGISCHEN EINGRIFP BEI EINWOHNERN SODINDIENS ZUSAMMENFASSUNG Es wurde festgestellt, dao Inder und Europaer in Siidindien wahrend der Narkose und des chirurgischen Eingriffes unterschiedlich reagierten. In einem Versuch zur Auswertung dieser Unterschiede wurden die Blutzuckerwene als ein MaOstab fiir die Reaktion des sympathischen Nervensystems herangezogen. Bei indischen Patienten trat eine starkere und langerdauernde Erhohung der Blutzuckerwerte unter der Allgemeinnarkose au fals bei Europaern in Indien oder England. Die Allgemeinnarkose selbst fiihrte noch zu keinem Anstieg sondern das Einsetzen des chirurgischen Traumas. Unter der Subarachnoidal- oder Epiduralanasthesie kam es wahrend des chirurgischen Eingriffes zu keinen grooeren Blutzuckerveranderungen. Im Verlauf der Untersuchung an insgesamt 4 Patienten kollabierten unerwartet drei Patienten, und wegen der SchockbekampfungsmaOnahmen waren die Ergebnisse der Blutzuckerbestimmung nicht verwertbar. Obwohl die Ernahrung^ eine gewifie Rolle spielen mag, werden die Unterschiede als rassisch und nicht klimatisch brdingt angesehen.