Epidural met-enkephalin (FK 33-824). A dose-effect study.
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Biomedical subjects
Publications and source records attributed to A Engquist.
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The adrenocortical, hyperglycemic, and hemodynamic responses to cholecystectomy or vagotomy were studied in 16 patients under halothane and N2O/O2 anesthesia. The patients were randomly divided into two groups: eight patients received naloxone in doses used clinically (2.5 microgram/kg i.v.) just before induction of anesthesia, while eight subjects received placebo. The results showed insignificant differences in plasma concentrations of cortisol and glucose between groups. Nor did blood pressure, heart rates, and inspired halothane concentrations differ significantly between groups. Thus, inhibition of opiate receptors and endorphins by naloxone in an otherwise clinically effective dosage does not influence the adrenocortical, hyperglycemic, or hemodynamic responses to surgical stress. We therefore conclude from our data that opiate receptors and endorphins are not involved in the initial phase of the endocrine-metabolic responses to surgery nor are they part of the neural mechanisms mediating stress-induced analgesia.
A 43-year-old male with bronchogenic carcinoma was treated with continuous morphine via a thoracic epidural catheter. On the fifth day, after a total dose of 24 mg morphine chloride in 10 or 20 ml saline, he developed hallucinations, hyperthermia, spasticity, narcolepsy and opisthotonos. Respiratory rate and blood pressure were unaffected. Intravenous naloxone reversed all neurological abnormalities. This unusual syndrome was probably caused by a rostal spread of morphine. The location of the catheter and volume seem to be important variables. Hallucinations are important signs of impending intoxication.
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The effects of neurogenic block on plasma concentrations of adrenaline, noradrenaline and cyclic AMP were studied. Eighteen patients were subjected to surgery of moderate or minor extent under enflurance anesthesia with or without epidural analgesia. The results show that adrenaline secretion during surgical stress is a response to neurogenic stimuli, since the increase found in patients subjected to hysterectomy under general anesthesia is blocked by the addition of epidural analgesia. Furthermore, plasma adrenaline after neurogenic block is comparable with adrenaline levels during minor surgical stress. The plasma noradrenaline concentration does not correlate with the extent of trauma. In contrast to adrenaline levels, noradrenaline concentrations varied insignificantly during and after surgery. However, the addition of epidural block induced a postoperative increase in noradrenaline apparently unrelated to changes in heart rate or blood pressure. Simultaneous measurements of the catecholamines and cyclic AMP indicate that adrenaline is of minor importance for plasma cyclic AMP in resting patients, whereas the increase in cyclic AMP elicited by surgery reflects adrenaline-stimulated beta-adrenergic activity.
The pathogenesis of the increased operative risk in elderly patients is unknown. From a theoretical point of view, a change in endocrine-metabolic response might be involved. In the present study, a battery of hormonal and metabolic variables were measured in eight young and eight elderly healthy males undergoing elective inguinal hernial repair under general anesthesia. Blood was drawn before induction of anesthesia, at skin incision, and one, two, and six hours after skin incision. The findings were: 1) Plasma cortisol increase was significantly higher in elderly than in young controls. 2) Plasma renin level was lower in old age, but renin-aldosterone and electrolyte response patterns were alike in the two groups. 3) Thyroid parameters, in terms of serum T4, serum T3, serum rT3, and T3-resin uptake, responded normally to surgery and showed no age-related differences. 4) The hyperglycemic response was not significantly influenced by age indicating unchanged glycoregulatory mechanisms also verified by determinations of plasma catecholamines, cAMP, and insulin. 5) Blood lymphocyte count was constantly lower in elderly than in young and decreased with time, but the age-related difference was not significant. 6) Blood polymorphonuclear leukocytes showed an increase of the same magnitude in both age groups, although at a significantly slower rate in the elderly. It is concluded that age affects some aspects of the initial endocrine-metabolic response to surgery.
The hypothalamic-pituitary-adrenocortical (HPA) responses to the hypoglycaemic stimulus and to operation (laparotomy) are compared. The studies were carried out in eight patients who were subjected to insulin-induced hypoglycaemia on the day before elective abdominal surgery. Plasma corticotrophin (ACTH) and plasma cortisol concentration increases were virtually indentical during the two procedures, which suggests that hypoglycaemia and surgical trauma are comparable stress factors and that the hypoglycaemia test is reliable in predicting the HPA responses to major surgical trauma.
Plasma concentrations of cyclic AMP, adrenaline and noradrenaline were measured in 6 patients undergoing hysterectomy from before induction of anaesthesia to 6 h after skin incision. Noradrenaline did not vary significantly during the observation period, whereas cyclic AMP and adrenaline increased after skin incision. A significant correlation was found between plasma concentrations of cyclic AMP and adrenaline (r = 0.84, P less than 0.01), suggesting that the latter is responsible for the increase in plasma cyclic AMP which is observed in relation to surgical procedures. Peak concentrations of cyclic AMP and adrenaline were seen in the early postoperative phase. This indicates that the most pronounced acute endocrine stress response to surgery of moderate severity occurs after termination of anaesthesia.
The renin-angiotensin system, ACTH and hyperkalaemia are known to induce increased plasma levels of aldosterone. In order to assess the relative significance of these mechanisms during surgical stress, aldosterone, cortisol and electrolytes in plasma were measured in 12 otherwise healthy women during and after cholecystectomy. The patients received either isotonic sodium chloride or 5 per cent glucose in water during the experimental period of 22 h. The results showed that the pronounced increase of aldosterone and the concomitant decrease of sodium in plasma found in patients given glucose in water could almost be inhibited by the administration of saline. Cortisol and potassium concentrations were identical in the two groups of subjects. It is concluded that the aldosterone response to surgery is mainly mediated via the renin-angiotensin system. This response is probably due to a reduced sodium content or volume of extracellular fluid, since it could almost be inhibited by administration of sodium chloride. The rationale of saline restriction during and after surgery is questioned.
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Cyclic AMP, glucose and cortisol in plasma were measured in three groups of patients undergoing hysterectomy. The operations were performed under general anaesthesia, under general anaesthesia combined with epidural analgesia and under epidural analgesia alone. Surgery elicited a significant rise in plasma cyclic AMP, glucose and cortisol when performed under general anaesthesia alone. Epidural analgesia extending from T4-6 to S5 combined with general anaesthesia abolished the rise in cyclic AMP and reduced the increase in glucose and cortisol and epidural analgesia alone extending from T4 to S5 blocked the rise in glucose and cortisol as well as that in cyclic AMP. The results support the theory that afferent nerve impulses from the area of trauma are of major importance for the catabolic state induced by surgical procedures and indicate that anaesthetic management which includes blockade of afferent nerve impulses which includes blockade of afferent nerve impulses from the area of trauma can be reduce the catabolic response to surgery. These observations could be of value in the operative management of patients with diabetes mellitus and possibly in other groups by patients with a high surgical morbidity.
The adrenocortical and hyperglycemic responses to hysterectomy were studied in five groups of patients receiving: general anesthesia (group I), general anesthesia + epidural analgesia extending from Th10-S5 (group II), general anesthesia + epidural analgesia extending from Th8-S4--5 (group III), general anesthesia + epidural analgesia extending from Th4--6-S5 (group IV) and epidural analgesia extending from Th4-S5 without general anesthesia (group V). The results showed that the cortisol response was abolished in group V, inhibited in group IV and normal in groups II and III. The hyperglycemic response to surgery was inhibited in groups II, III and IV, and abolished in group V. Epidural analgesia from Th4 to S5, preventing the adrenocortical and hyperglycemic responses to hysterectomy, and possibly also inhibiting other components of the endocrine-metabolic response to surgery, may have important applications in further studies of the physiologic significance of the endocrine-metabolic response to surgery.
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Blood clot lysis time (BLT) and plasma cortisol concentration were measured during major abdominal surgery in 15 unsupplemented glucocorticoid-treated patients. Eight patients showed an impaired cortisol response and seven patients had normal cortisol concentrations when compared with the cortisol response of 23 control patients with normal pituitary-adrenal function. There was no statistically significant difference between variations of BLT in the group of patients with impaired cortisol response and patients with normal cortisol concentrations. It is concluded that stress-induced activation of blood fibrinolysis is coincidental with, but independent of, adrenocortical activity.