Circulating tetrahydrobiopterin concentrations in patients with septic shock

Nitric oxide synthase requires tetrahydrobiopterin for its activity.In animal models of sepsis, changes in circulating tetrahydrobiopterinconcentrations precede increases in nitrate. We measured plasmatetrahydrobiopterin and nitrate concentrations on three consecutivedays in 10 patients with septic shock and 10 critically illcontrol patients. Total nitrate concentration was measured afterreduction of nitrite to nitrate. Tetrahydrobiopterin concentrationswere measured using HPLC. The median (range) APACHE II scorewas 22 (13–27) in the patients with septic shock and 25(7–28) in the control group. The nitrate concentrationwas significantly higher in patients with septic shock thanin controls (P=0.01) on all days but did not change with time.Tetrahydrobiopterin concentrations were highest in the patientswith septic shock on day 1 only (P=0.037). In the seven patientswith renal failure, both nitrate and tetrahydrobiopterin concentrationstended to be higher than in the 13 patients without renal failure.The nitrate concentration correlated with tetrahydrobiopterinconcentration on day 1 only (P=0.05). In patients with septicshock, both tetrahydrobiopterin and total nitrate concentrationswere higher than those in critically ill controls but were increasedmainly in patients with renal failure. In summary, tetrahydrobiopterinconcentration increases during septic shock, in line with increasesin nitrate concentration. However, as for nitrate, concentrationsare affected by renal function. Measurement of tetrahydrobiopterinconcentration is extremely technically demanding and time consumingand offers no advantage over measurement of nitrate concentration. Br J Anaesth 2001; 86: 578–80