Twenty-eight patients presenting for aortic surgery were randomly assigned in a double-blind, placebo-controlled protocol to receive placebo (n = 14) or clonidine (4.7 +/- 1.2 micrograms.kg-1 po; n = 14), in addition to flunitrazepam 120 min before induction of anesthesia. Plasma catecholamines (CA) and hemodynamic variables were determined at 7 stages during surgery. In the placebo group, plasma epinephrine (E) and norepinephrine (NE) had risen twofold at skin closure compared to baseline (E: from 109 +/- 51 pg.ml-1 to 294 +/- 161 pg.ml-1; NE: from 658 +/- 226 to 1150 +/- 494 pg.ml-1). Plasma CA were significantly lower in the clonidine group (P less than 0.001 and 0.01 vs placebo for NE and E respectively). In both groups, similar directional changes were observed for the circulatory variables, upon aortic clamping and declamping. In the clonidine group, however, mean arterial pressure was lower at most stages (P less than 0.05 vs placebo); moreover, stroke volume index was greater in the clonidine group (P less than 0.05) upon declamping. This improved stability in the clonidine group was achieved with a halving in the number of anesthetic/circulatory interventions (P less than 0.05 vs placebo). Provided intravascular volume is adequate, clonidine suppresses the increase in plasma catecholamines induced by aortic surgery and improves circulatory stability, with a reduced number of anesthetic, circulatory adjustments.

No abstract

After completion of abdominal aortic graft, 29 patients received an i.v. infusion of placebo (n = 16) or clonidine 7 micrograms kg-1 (n = 13) over 120 min in a double-blind study. Cardiovascular variables were measured and plasma samples obtained up to 5 h after arrival in the recovery room, for assay of noradrenaline, adrenaline, vasopressin and renin concentrations. Noradrenaline, adrenaline and vasopressin concentrations decreased in the clonidine group throughout recovery (P less than 0.001, 0.05 and 0.05, respectively, vs placebo). Heart rate was less in the clonidine group (P less than 0.01). There was no significant difference in mean arterial pressure between groups. Stroke volume was larger (P less than 0.01) and there were fewer episodes of hypertension (P less than 0.05) and tachycardia in the clonidine group. In addition, a reduction in the number of circulatory interventions (P less than 0.05) and episodes of shivering was noted in the clonidine group. Mean (SD) postoperative volume requirements were larger in the clonidine group (total postoperative input: clonidine 1462 (604) ml; placebo 1064 (348) ml (P less than 0.05]. These data are consistent with the observation that clonidine modifies endocrine and circulatory status after major surgery.

Histamine was infused in six normal volunteers at rates of 16, 32, 64 and 96 ng/kg/min increasing at 5-min intervals followed by 128 ng/kg/min for 45 min. Heart rate increased, diastolic blood pressure decreased and skin temperature increased in a dose-dependent fashion. Mean heart rate increased by 15.6 +/- 5.7 beats/min, mean diastolic pressure fell by 8.8 +/- e.2 mmHg and mean skin temperature increased by 1.2 +/- 0.3 degrees C at the highest infusion rate. Mean plasma histamine rose from a basal level of 0.20 +/- 0.03 ng/ml to 1.97 +/- 0.25 ng/ml at the end of the highest infusion rate. The threshold infusion rate for physiological effects was 64-96 ng/kg/min corresponding to 0.77-0.97 ng/ml. Salivary flow was stimulated by 21% after 30 min at the highest dose infusion (P = 0.05). Plasma adrenaline increased 132% but plasma noradrenaline was unchanged. There was a linear decline in heart rate after terminating the histamine infusion with a half time of 82 sec. The half life of infused histamine in the plasma was 102 sec. The clearance of histamine from the plasma was 6.1 %/- 0.2 l/min or 83 ml/kg/min. These concentration effect relationships in normals throw doubt on some of the high endogenous plasma histamine values in the literature.

To determine whether small changes in sympathetic activity would cause detectable changes in plasma norepinephrine (NE) levels, and whether the effects of endogenously released and exogenous NE differ, we injected tyramine infusions and l-norepinephrine (l-NE), into six healthy subjects, and the changes in blood pressure (BP) and plasma NE were related. The mean increase in systolic BP was approximately 17 mm Hg with both infusions; diastolic BP increased with l-NE but did not rise significantly with tyramine. Heart rate fell more with l-NE than with tyramine infusions. The maximum increase in plasma NE levels was more than 500% during l-NE infusions but less than 200% with tyramine. There was no correlation between plasma NE and absolute levels of systolic BP when individual data were plotted for tyramine infusions, whereas mean group changes in systolic BP correlated strongly with mean group plasma NE, both during tyramine and l-NE infusions. The slope of the relationship was much steeper for tyramine than for l-NE. We conclude that the use of plasma NE to measure small differences in sympathetic activity among individuals is limited by interindividual variability, whereas changes in sympathetic activity within groups are more likely to be detected.