Spinal epidural abscesses - The role for non-operative management: A systematic review.

BACKGROUND: Spinal Epidural Abscesses (SEAs) are traditionally seen as a surgical emergency. However, SEAs can be discovered in entirely asymptomatic patients. This presents a dilemma for the attending clinician as to whether to subject these patients to significant surgery. This systematic review updates the evidence surrounding the efficacy of non-operative SEA management by means of intravenous antibiotics ± radiologically-guided aspiration. AIMS: 1. To assess failure rates of medical therapy for SEA. The absolute definition of 'failure' used by the study was recorded, and comparisons made. 2. To review of risk factors for success/failure of medical treatment for SEA. METHODS: A database search with the MESH term 'epidural abscess' and keywords ['treatment' OR 'management'] were used. RESULTS: 14 studies were included. The number of SEA patients managed non-operatively ranged from 19 to 142. There was significant heterogeneity across the studies. Pooled Failure of Medical Therapy (FMT) (defined as any poor outcome) was 29.40%. When FMT = mortality the pooled rate was 11.49%. Commonly cited risk factors for FMT included acute neurological compromise, diabetes mellitus, increasing age and Staphylococcus aureus. CONCLUSION: SEA will always be a condition mostly managed surgically. Despite this, there is growing evidence that non-operative management can be possible in the correct patients. The key is in patient selection - patients with any of the above-mentioned risk factors have the potential to deteriorate further on medical treatment and have a worse outcome than if they had undergone emergency surgery straight away. Ongoing research will hopefully further investigate this crucial step.

The binding of low molecular weight heparin to hemostatic enzymes.

A low molecular weight preparation of porcine heparin (specific anticoagulation activity = 125 units/mg) was fractionated to obtain a mucopolysaccharide product of 6500 daltons (specific anticoagulant activity = 373 units/mg) that is homogeneous with respect to its interaction with antithrombin. This material was treated with fluorescamine in order to introduce a fluorescent tag into the mucopolysaccharide. Initially, we showed that the fluorescamine-heparin conjugate and the unlabeled mucopolysaccharide interacted with antithrombin in a virtually identical fashion. Subsequently, we demonstrated that labeled heparin could be utilized in conjunction with fluorescence polarization spectroscopy to monitor the binding of mucopolysaccharide to thrombin, factor IXa, factor Xa, and plasmin. The interaction of this complex carbohydrate with thrombin exhibited a stoichiometry of 2:1 with KH1T DISS = KH2T DISS = 8 x 10(-7) M. The formation of mucopolysaccharide . factor IXa complex is characterized by a stoichiometry of 1:1 with KHIXa DISS = 2.58 x 10(-7) M. The binding of heparin to factor Xa or plasmin occurred with low avidity. Therefore, the stoichiometries of these processes could not be established. However, our experimental data were compatible with a single-site binding residue with KHXa DISS = 8.73 x 10(-6) M and KHPL DISS = approximately 1 x 10(-4) M, respectively.

The kinetics of hemostatic enzyme-antithrombin interactions in the presence of low molecular weight heparin.

The kinetics of inhibition of four hemostatic system enzymes by antithrombin were examined as a function of heparin concentration. Plots of the initial velocity of factor Xa-antithrombin or plasmin-antithrombin interaction versus the level of added mucopolysaccharide exhibit an ascending limb and subsequent plateau regions. In each case, the kinetic profile is closely correlated with the concentration of the heparin . antithrombin complex formed within the reaction mixture. A decrease in the velocity of inhibition is not observed at high levels of added mucopolysaccharide despite the generation of significant quantities of heparin-enzyme interaction products. The second-order rate constants for the neutralization of factor Xa or plasmin by the mucopolysaccharide . inhibitor complex are 2.4 x 10(8) M-1 min-1 and 4.0 x 10(6) M-1 min-1, respectively. These parameters must be contrasted with the similarly designated constants obtained in the absence of heparin which are 1.88 x 10(5) M-1 min-1 and 4.0 x 10(4) M-1 min-1, respectively. Plots of the initial velocity of the factor IXa-antithrombin or the thrombin-antithrombin interaction versus the level of added mucopolysaccharide exhibit an ascending limb, pseudoplateau, descending limb, and final plateau regions. In each case, the ascending limb and pseudoplateau are closely correlated with the concentration of heparin c antithrombin complex formed within the reaction mixture. Furthermore, the descending limb and final plateau of these two processes coincide with the generation of increasing amounts of the respective mucopolysaccharide-enzyme interaction products. The second-order rate constants for the neutralization of factor IXa or thrombin by the heparin . antithrombin complex are 3.0 x 10(8) M-1 min-1 and 1.7 x 10(9) M-1 min-1, respectively. The second-order rate constants for the inhibition of mucopolysaccharide-factor IXa or mucopolysaccharide-thrombin interaction products by the heparin . antithrombin complex are 2.0 x 10(7) M-1 min-1 and 3.0 x 10(8) M-1 min-1, respectively. These kinetic parameters must be contrasted with similarly designated constants obtained in the absence of mucopolysaccharide which are 2.94 x 10(4) M-1 min-1 and 4.25 x 10(5) M-1 min-1, respectively. Thus, our data demonstrate that binding of heparin to antithrombin is required for the mucopolysaccharide-dependent enhancement in the rates of neutralization of thrombin, factor IXa, factor Xa, or plasmin by the protease inhibitor. Furthermore, a careful comparison of the various constants suggests that the direct interaction between heparin and antithrombin may be largely responsible for the kinetic effect of this mucopolysaccharide.

Multiple functional domains of the heparin molecule.

Affinity-fractionated porcine heparin was randomly scissioned by chemical techniques to give hexasaccharides, octasaccharides, decasaccharides, and mucopolysaccharide fragments of approximately 14 residues and approximately 16 residues that were able to complex with the protease inhibitor. Direct measurements of the kinetic behavior of the hexasaccharides, octasaccharides, and decasaccharides showed that these fractions greatly enhanced the rate of Factor Xa inactivation by antithrombin. Indeed, these species exhibited specific molar activities that ranged from 6.9% (hexaccharide) to 60.9% (decasaccharide) of that of the heparin fragment of approximately 16 residues. However, these oligosaccharides exhibited essentially no ability to accelerate thrombin-antithrombin interactions. The avidity of the hexasaccharides, octasaccharides, and decasaccharides for the protease inhibitor increased as a function of size with the respective dissociation constants ranging from 5.5 X 10(-6) M to 2.9 X 10(-7) M. These data suggest that the region of the heparin molecule needed for catalyzing Factor Xa-antithrombin interaction is intimately related to the antithrombin binding domain. The smallest complex carbohydrate fragment that accelerated the inactivation of thrombin by antithrombin had approximately 14 residues. This fraction had an avidity for the protease inhibitor of 2.8 X 10(-7) M and specific molar activities of 140 units per mumol (thrombin neutralization) and 460 units per mumol (factor Xa inactivation). The largest heparin fragment examined contained approximately 16 residues. This fraction had an avidity for antithrombin of 2.4 X 10(-7) M and specific molar activities of 500 units per mumol (thrombin neutralization) and 560 units per mumol (Factor Xa inactivation). Detailed kinetic analyses showed that these two species are able to directly activate antithrombin to the same extent with respect to thrombin inhibition. However, the larger mucopolysaccharide fragment is also capable of approximating free enzyme with protease inhibitor.