The antidotal action of thiosulfate following acute nitroprusside infusion in dogs.

The authors previously demonstrated in dogs that a bolus dose of sodium thiosulfate maintained enhanced cyanide metabolism throughout a 1-h infusion of sodium nitroprusside (SNP). To further test this antidotal action, a bolus dose of thiosulfate (150 mg . kg-1) was given to eight dogs at the end of a 60-min near-lethal infusion of nitroprusside (3 mg . kg-1). Within 2 min of the antidote, mean plasma thiocyanate levels (70.3 mumol . l-1) were significantly higher than those of seven control dogs given nitroprusside only (45.9 mumol . l-1, P = 0.002) and plateaued at 153.8 mumol . l-1 within 60 min, while the control values only reached 79.1 mumol . l-1 (P less than 0.001). Although differences between plasma cyanide levels in the two groups only attained significance 1 h after administering the antidote (0.8 vs. 2.74 mumol . l-1, P = 0.03), red blood cell cyanide concentrations were significantly lower in the antidote group within 5 min (166 vs. 225 mumol . l-1, P = 0.004) and remained so throughout the 2-h observation period. Compared with the controls, there was an impressive reduction in mean half-lives of plasma cyanide (25.1 vs. 74.1 min) and red blood cell cyanide (22.4 vs. 203.6 min). Similarly, peak cyanide levels occurred much sooner following the antidote (mean times: plasma cyanide 2.9 vs. 5.9 min; red blood cell cyanide 0.25 vs. 11 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cyanide antidotes used with sodium nitroprusside infusions: sodium thiosulphate and hydroxocobalamin given prophylactically to dogs.

Cyanide antidotes were given to dogs before an infusion of sodium nitroprusside 1.5 mg kg-1 for 1 h. Dogs given thiosulphate 75 mg kg-1 had significantly lower plasma and red cell cyanide concentrations while plasma thiocyanate concentrations were significantly increased in comparison with control. These changes were associated with only minimal disturbance of tissue oxygenation. There was no effect on red cell cyanide or thiocyanate concentrations in dogs treated with hydroxocobalamin 1.5 mg kg-1, but plasma cyanide concentrations were significantly greater than in those receiving no antidote although there was less evidence of impaired oxygenation. There was no evidence of a synergistic action between thiosulphate and hydroxocobalamin. The vascular response to nitroprusside was unchanged in the thiosulphate-treated dogs, but was significantly greater in those given hydroxocobalamin. The implications for prophylaxis and treatment of cyanide poisoning following nitroprusside overdose are discussed.

Blood concentrations of nitrous oxide in theatre personnel.

Blood concentrations of nitrous oxide were measured in anaesthetists, surgeons and theatre nurses. Comparison of anaesthetists and surgeons working in the same theatre showed that in ENT surgeons concentrations were greater (P < 0.01), while in general surgeons they were smaller (P < 0.003). Blood concentrations of nitrous oxide in the "circulating" nurses were low; with scavenging they were unmeasurable. Atmospheric concentrations in the breathing zones were usually greater than the corresponding blood concentrations, but this was not always true. However, a positive correlation between blood and atmospheric concentrations was obtained (r = 0.82). Meticulous use of scavenging devices produced a mean reduction in blood nitrous oxide concentrations of 86% for all groups. The mean blood concentration of nitrous oxide in anaesthetists when scavenging was used was 45 p.p.m. (1.9 micromol/litre). This figure should be taken into account in establishing maximum permitted exposure to nitrous oxide.

The effects of sodium nitroprusside and cyanide on haemoglobin function.

Incubation of human blood with 0.3 mM sodium nitroprusside (SNP) or 1 mM potassium cyanide (KCN) for 180 min produced a 600-fold increase in red cell cyanide concentration, a 4% decrease in oxygen capacity and a 6% increase in oxygen affinity. These effects were not reproduced in patients receiving SNP by infusion probably because in the clinical situation much smaller amounts of the drug were used and red cell cyanide levels were lower. The in vitro observations could be explained by cyanide either combining directly with the haemoglobin or encouraging its spontaneous oxidation to methaemoglobin during the incubation. Differences in distribution of cyanide between red cell and plasma following incubation with SNP or KCN and the initial lag phase in accumulation of cyanide in the red cell with SNP provide further evidence that nitroprusside breaks down principally within the red cell.

An evaluation of the clinical potential of a comprehensive model of human respiration in artificially ventilated patients.

1. We have investigated the feasibility of accurately simulating the respiratory function of artificially ventilated patients, using a computer model of the respiratory system. Twelve patients artificially ventilated after uncomplicated cardiac bypass surgery was studied. 2. The basic information required to simulate individual ventilated subjects was measured or derived. A program was written to enable key model parameters to be adjusted automatically to match model predictions to these clinical measurements. On completion of this matching procedure all the variables computed by the model were compared with patient values (measured or derived) and their accuracy was assessed. 3. The matching algorithm successfully optimized parameters of the model representing metabolic activity, tissue respiratory quotient, venous admixture, physiological dead space and total body bicarbonate to match measured values for oxygen consumption, carbon dioxide production, Pa, O2, PaCO2, and arterial HCO3- respectively. Other variables compared arise from the solution of equations within the model and correlation between model and patient values is generally good (r greater than 0.9). However, values of Pv-, O2 correlate less well (r = 0.85). Factors affecting the accuracy of patient simulation are discussed and some deficiencies analysed. 4. The creation of an accurate, steady-state representation of a patient by the model opens up the possibility of using it interactively as an aid to clinical management. Some possible future developments of the technique are discussed.