Effects of clonidine on the pituitary hormonal response to pelvic surgery

Abstract

We have investigated the effects of the central alpha 2 adrenoreceptor agonist, clonidine, given i.v. before induction of anaesthesia, on the haemodynamic and endocrine responses to pelvic surgery. Twenty patients were allocated randomly to receive either clonidine 3 micrograms kg-1 or an equivalent volume of 0.9% sodium chloride solution. Arterial pressure, heart rate, and circulating concentrations of cortisol, growth hormone, glucose and lactate were measured during and in the 24 h after total abdominal hysterectomy. Arterial pressure and heart rate decreased significantly in the clonidine group during surgery and in the early postoperative period. There were no differences between groups in serum cortisol or growth hormone concentrations throughout the study. Despite an effective decrease in the cardiovascular response to surgery, clonidine 3 micrograms kg-1 i.v. had no significant effect on pituitary hormone secretion.

Low dose clonidine premedication accentuates the hyperglycemic response to surgery

“…1,2 In contrast, clonidine administration of 3 µg·kg -1 caused a more pronounced increase in glucose plasma concentration during abdominal hysterectomy without affecting pituitary hormone secretion or plasma cortisol. 3 Although insulin plasma concentrations were not measured, the hyperglycemic action of clonidine observed in that study was attributed to the inhibitory effect of clonidine upon the ß cells of the pancreas and decreased insulin release. In the present study, low dose clonidine premedication was also associated with a higher plasma glucose concentration compared with the control group 60 min after peritoneal incision, i.e., 90 min after iv administration, when the maximum effect is expected.…”

“…2 In contrast, iv clonidine administered at a lower dose caused a more pronounced increase in glucose plasma concentration during pelvic surgery. 3 It was hypothesized that the hypoglycemic action of clonidine secondary to sympathoadrenergic inhibition can be overcome by a direct inhibitory effect on the ß cells of the pancreas and insulin secretion as shown in in vitro experiments. 4 It seems that the influence of clonidine on the surgical stress response is variable depending on the dose administered and the type of surgery studied.…”

“…3 Using Student t-test and considering an expected mean difference in glucose plasma concentration of 15% between the groups (power 80%, = 5%), a total of eight patients was calculated to be sufficient.…”

“…12 The attenuation of the cortisol response by clonidine in our study is in contrast to the results of previous investigations reporting no modifying effect of clonidine administered at a higher dose (2 or 3 µg·kg -1 ) in unpremedicated patients undergoing abdominal hysterectomy. 3,13 It has to be noted, however, that all patients entering the present study protocol received oral premedication with benzodiazepines (20 mg chlorazepate) the night prior to surgery and three hours before the operation, which per se affects perioperative ACTH and cortisol plasma concentrations. 14 We conclude that premedication with clonidine administered at a dose insufficient to inhibit the surgery induced stimulation of sympathoadrenergic pathways, accentuates the hyperglycemic response to surgery most likely mediated through its inhibitory effect on insulin secretion.…”

Physiologic kinetic profile of glycemic response in a single dose of clonidine

“…[5] As such, this justifies the suppressive effects of clonidine in the release of catecholamine and better glucose regulation during stressful conditions. However, clonidine and its derivatives have similar reaction patterns as these substances were found to be sedative and increased blood glucose levels [6] even at low doses, [7] but hyperglycemic responses were suppressed at higher doses. [8] Both intracisternal and intravenous clonidine administrations resulted to hyperglycemia reflecting variations in the mechanisms on its central and peripheral effects.…”