Effects of oral clonidine premedication on concentrations of Cortisol and monoamine neurotransmitters and their metabolites in cerebrospinal fluid and plasma

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Abstract
Forty-two male patients (aged 19-40 years), undergoing orthopaedic surgery under spinal anaesthesia (3 ml isobaric 0.5% bupivacaine), were given clonidine 4.5 .mu.g kg-1 orally either 2 (Group I, n = 10) or 4 (Group II, n = 10) hours before the operation, diazepam 0.15 mg kg-1 orally (Group III, n = 10) or a placebo tablet (Group IV, n = 12) 2 h before the operation. Plasma concentrations of cortisol, noradrenaline (NA), adrenaline (A), 3,4-dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC) were assayed from venous blood samples just before premedication and just before the spinal block. Cerebrospinal fluid (CSF) concentrations of cortisol, tryptophan, 5-hydroxyindoleacetic acid and catecholamine metabolites were assayed from a sample taken before the spinal block. The plasma NA concentrations of the patients in the groups receiving clonidine decreased clearly compared with the other groups (P < 0.05). The NA metabolite DHPG was also lower in Groups I and II than in Group III (P < 0.05) after premedication. Plasma A concentrations were lower in Groups I and III than in Group IV (P < 0.05). The CSD concentrations of the different substances were similar in all groups. In group I the sensory blockade lasted significantly longer than in Group III (P < 0.05) and the mean duration of motor blockade was longer in Group I than in groups III and IV (P < 0.05). Two patients in both clonidine groups developed bradycardia (heart rate < 45 min-1) requiring atropine treatment. The mean lowest heart rate was lower in Group I than in Groups III and IV (P < 0.05). The patients in Group II were more sedated than those in Group IV (P < 0.05), but the degree of fear was similar in all groups. No correlations were found between sedation or fear and the level of any of the hormones or metabolites.