Clinical Features of Fluid Retention Complicating Treatment with Guanethidine.

IN the course of a clinical trial of the hypotensive drug guanethidine, it was observed that a proportion of treated patients developed edema or an unexplained gain in weight, thought to be a result of fluid retention.' This observation was confirmed when Dollery, Emslie-Smith, and Milne2 reported a further series, noting fluid retention yet being unable to correlate it with any diminution in the urinary excretion of sodium or water in the two patients they studied by balance technics. The association of fluid retention and temporary loss of blood pressure control, both easily reversed by diuretic drugs, was later reported in more detail.3 A review of the literature on hypotensive drug treatment reveals many reports of similar fluid retention occurring with a range of different drugs. Perera,4 5 MacArthur,6 Melick and McGregor,7 and Winer8 reported and investigated this side effect during treatment with reserpine while Fraser and Lowe9 and Ronnov-Jessen'0' 11 recorded its production by ganglion-blocking drugs. More recently, alphamethyl dopa has also been shown to have fluid-retaining properties.12' 13 It has been variously assumed that progressive impairment of renal function resulting from postural hypotension, venous pooling in the extremities, or reduction in cardiac output was responsible, either singly or in combination, for this inconvenient and occasionally dangerous side effect. R0nnovJessen'0 emphasized the renal factors when he stated: "it is possible that the reduction in the blood pressure prevents an affected kid-