Hip dislocation in patients with multiple injuries. A followup investigation.

The combination of traumatic hip dislocation and multiple trauma have not been well documented in the medical literature to date. The role of surgery therefore has not been well defined in these patients. During a 12-year period, 29 consecutive patients with 31 traumatic hip dislocations with concomitant Injury Severity Scores exceeding 18 points were treated at the authors' institution. An initial satisfactory closed reduction was achieved in 23 patients, two patients had failed reductions, and four patients had noncongruous reductions. Open surgical procedures were done on these patients and on 10 additional patients who had associated acetabular or femoral head fractures. Overall, seven patients from the group died including two patients who had surgical procedures. From 17 living patients who did not require surgery for failed or noncongruous reductions, 13 patients were available for followup at a mean of 8 years after their injury. The clinical results at this followup were excellent in three hips, good in seven hips, and fair in four hips. The radiologic results, however, showed that five patients had early (Grades I and II according to Matta) hip degeneration and seven patients had Grade II (according to Ficat) avascular necrosis of the femoral head. These changes were not clinically significant at this followup and it is proposed that these results justify a policy of active treatment of traumatic hip dislocation in patients with multitrauma.

Kinetics and metabolism of sulfinpyrazone.

Six normal subjects (three men and three women) took 200 mg sulfinpyrazone in two oral preparations, a capsule and a suspension. Plasma and urine levels of sulfinpyrazone and the sulfide, p-hydroxy, and sulfone metabolites were measured over three days. The plasma sulfinpyrazone/time concentration profiles indicated a postabsorptive biexponential decline with a mean terminal half life (t1/2) of 299 +/- 107 min. There was intersubject variation in the formation of the metabolites, the greatest being with the sulfide metabolite. Mean t1/2 of the sulfide metabolite was 659 +/- 192 min. The apparent fraction of sulfinpyrazone absorbed was 0.93 +/- 0.24 and the free fraction in plasma was 1.26 +/- 0.04%. Since the sulfide metabolite has a more potent antiplatelet effect and its formation in normal subjects is variable, direct administration of the sulfide may provide a more predictable antithrombotic effect in patients.

Dipyridamol kinetics.

The kinetics of the antiplatelet drug dipyridamole were studied in six normal subjects (three men and three women) who were ages 22 to 34 yr old. Each received 20 mg IV and four also took a 50-mg oral dose. Blood samples were collected after each dose for a period of 3 days and concentrations of dipyridamole were measured by a sensitive and specific high-performance liquid chromatographic assay. Concentrations after the intravenous dose showed a triexponential decline with a terminal half-life of 11.6 +/- 2.2 hr (x +/- SD). Total plasma clearance was 8.27 +/- 1.82 1/hr and the apparent volume of distribution was 141 +/- 51 1. Concentrations rose 6 to 10 hr after intravenous dipyridamole in each female subject, but not in the male subjects. Dipyridamole blood/plasma concentration ratio changed from an average of 0.7 over the first hour to 1.2 after 5 hr after the intravenous dose. There was an absorption lag time ranging from 34 to 75 min after the oral dose; concentrations peaked at about 2 to 2.5 hr after the dose. The percentage of unbound drag in plasma was 0.88 +/- 0.24%. Systemic availability of the end oral dose was 43 +/- 13%. These results suggest widely varying concentrations in patients receiving the drug, and raise questions about the current clinical practice of using empirical dosage schedules.

Heparin kinetics determined by three assay methods.

Heparin kinetics were determined in four normal subjects, each of whom received three different doses (25, 50, and 75 units/kg body weight) by intravenous injection. Multiple blood samples were collected after each dose and each plasma sample was assayed for heparin activity using three different assay methods. Two of these assays are based on coagulation tests, i.e., activated partial thromboplastin time and thrombin time, while the third is based on chemical neutralization of heparin using hexadimethrine bromide. Heparin kinetics showed pronounced dose-dependent changes, irrespective of the assay method used, which were characterized by increasing biologic half-life and decreasing total clearance (Cl) with increasing dose. No changes were noted in apparent volume of distribution (Vd). This data also showed that there were differences in kinetic parameters of heparin depending on the assay method. In general, values for total Cl and apparent Vd based on chemical neutralization were approximately 1.5 to 2.0 times these parameters based on coagulation tests. We conclude that the immediate mechanism of the dose-dependent heparin kinetics is decreasing total clearance with increasing dose and suggest that in vivo activation of the anticoagulant properties of heparin may explain the assay-dependent kinetics.

Intersubject variability in the anticoagulant response to heparin in vitro.

The significance of baseline coagulation times and plasma concentrations of serine protease inhibitors as determinants of the relationship between heparin activity and its anticoagulant effect has been investigated in vitro. Citrated plasma was prepared from blood obtained from 20 normal subjects, and heparin added to yield concentrations ranging from 0.05 to 1.5 units/ml. The anticoagulant effect was determined by the activated partial thromboplastin time (APTT) and thrombin time (TT). An excellent linear relationship was observed between the natural logarithms (ln) of the coagulation times and heparin activity. Baseline APTT values ranged from 28.4 to 59.7 s and the slope values for the ln APTT vs heparin curves ranged from 1.488 to 3.427 ml/unit. Similar range was observed in the slope values for the ln TT vs heparin curves. There was a highly significant positive correlation between the ln APTT vs heparin slope values and the baseline APTT values (r: 0.905; p less than 0.001). There was also a weak but statistically significant positive correlation between plasma concentrations of alpha 2 macroglobulin and baseline APTT values (0.02 greater than 0 greater than 0.01) and slope values of the ln APTT vs heparin curves (0.02 greater than p greater than 0.01). Furthermore, there was a statistically significant positive correlation between plasma concentrations of alpha 1 antitrypsin and baseline TT values (0.05 greater than p greater than 0.02) and slope values of the 1n TT vs heparin (0.02 greater than p greater than 0.01). Neither baseline APTT and TT values nor slope values of the ln APTT and TT vs heparin curves were statistically significantly related to plasma concentrations of antithrombin III, fibrinogen, or alpha 1 acid glycoprotein. This study has demonstrated that baseline APTT is a major determinant of the anticoagulant response to heparin in vitro, as determined by that same coagulation test, and it illustrates that there is a wide intersubject variation in the anticoagulant response to heparin in vitro.

High-performance liquid chromatographic analysis of dipyridamole in plasma and whole blood.

A rapid, sensitive, and specific high-performance liquid chromatographic method is described for the quantitative analysis of dipyridamole in plasma and whole blood. The method involves a single extraction of an alkalinized sample with diethyl ether followed by evaporation of the organic solvent and ion-pair chromatography using fluorescence detection. The lower limit of sensitivity for dipyridamole is 1 ng/ml. Concentrations of dipyridamole between 1 and 500 ng per sample are measured with an average coefficient of variation of 4.5% in plasma and 7.4% in whole blood.

High-performance liquid chromatographic analysis of sulfinpyrazone and its metabolites in biological fluids.

A rapid, senstivie, and specific high-performance liquid chromatographic method is described for the quantitative analysis of sulfinpyrazone and its sulfone and p-hydroxy metabolites in plasma and urine. The method uses two different procedures for sample preparation: (1) a rapid and convenient procedure using a single extraction with 1-chlorobutane and subsequent back-extraction into sodium hydroxide solution for the analysis of sulfinpyrazone and its sulfone metabolite, and (2) a more time consuming procedure using triple extraction with ethylene dichloride, a buffer wash, and back extraction into the base for the additional analysis of the p-hydroxy metabolite. The lower limit of sensitivity for fulfinpyrazone is 50 ng/ml. Concentrations of sulfinpyrazone between 0.05 and 0.1 and 50 micrograms/ml were measured with an average coefficient of variation of 3.9%, ranging from 1.5 to 6.1%.