Diuretic effect of clonidine during isoflurane, nitrous oxide, and oxygen anesthesia

Because clonidine, a relative selective alpha 2-agonist, inhibits the action of arginine vasopressin (AVP), the authors examined whether clonidine as an oral preanesthetic medication would induce diuresis and also would affect AVP release and its action during general anesthesia.

Fifty-seven patients (aged 18-65 yr) randomly received oral clonidine either approximately 5 micrograms.kg-1 (n = 19), approximately 2.5 micrograms.kg-1 (n = 19), or none (n = 19) in addition to oral famotidine 20 mg, 90 min before arrival at operating room. Urine volume, urine osmolality, and amount of sodium and potassium excreted into urine were examined every hour for 3 h during minor surgery under general anesthesia with isoflurane and nitrous oxide in oxygen. For 5 patients of each group, plasma AVP and atrial natriuretic peptide concentrations and urine cyclic adenosine monophosphate concentrations as an index of AVP action were also assayed.

Urine output indices (calculated as hourly urine output [milliliters per hour] divided by body weight [kilograms]) were significantly greater in the all periods (P < or = 0.035) after the initiation of anesthesia in the patients receiving clonidine 5 micrograms.kg-1 and only in the 3rd h in those receiving clonidine 2.5 micrograms.kg-1 (P = 0.047) as compared with those in the patients given famotidine alone. The peak effects of diuresis and natriuresis induced by oral clonidine 5 micrograms.kg-1 were both observed at the 2nd h (mean +/- SEM, 2.4 +/- 0.4 ml.kg-1.h-1 and 5.7 +/- 1.5 mEq.h-1 vs. 0.6 +/- 0.1 ml.kg-1.h-1 and 2.2 +/- 0.5 mEq.h-1 in the control subjects; P = 0.001 and P = 0.049). Kaliuresis also increased in the patients receiving clonidine 5 micrograms.kg-1 in the 2nd and 3rd h (P < or = 0.003). Urine osmolality showed a significant reduction over time in patients given clonidine but not in the control subjects. However, plasma AVP and atrial natriuretic peptide levels, and urine cyclic adenosine monophosphate concentrations did not significantly differ among the three groups.

Oral preanesthetic medication of clonidine 2.5 or 5 micrograms.kg-1 caused a significant diuretic effect during surgery under general anesthesia, though it did not apparently relate to AVP action. This effect of clonidine could be related to its pharmacological action as an alpha 2-adrenoceptor agonist not necessarily restricted to the kidney. The diuretic effect of clonidine implicates its clinical importance in the management of patients during anesthesia.