ABSTRACT
Local anesthetic toxicity is a rare, but potentially lethal, complication of regional anesthesia that cannot be prevented by any single measure. It is associated with CNS excitation and can lead to refractory cardiac dysfunction and collapse. The development of lipid emulsion for the treatment of anesthetic-induced toxicity resulted from a set of observations during a study on the potent, lipophilic drug bupivacaine and its associated clinical risk of intransigent cardiac toxicity in otherwise healthy individuals. Subsequent laboratory studies and clinical reports have shown that infusion of lipid can reliably reverse toxicity from potent local anesthetics as well as other drugs. The underlying mechanisms of lipid resuscitation may be a combination of a 'lipid sink' and metabolic effect. Lipid rescue has led to a reduction in fatalities associated with severe systemic toxicity, but continued research is necessary for a better mechanistic understanding. Increased physician awareness and education, as well as optimized treatment protocols, will significantly reduce the rate of morbidity and mortality from local anesthetic toxicity.
Subject(s)
Anesthesia, Conduction/adverse effects , Anesthetics, Local/adverse effects , Bupivacaine/adverse effects , Fat Emulsions, Intravenous/therapeutic use , Heart Arrest/drug therapy , Anesthetics, Local/administration & dosage , Anesthetics, Local/toxicity , Animals , Bupivacaine/administration & dosage , Bupivacaine/toxicity , Disease Models, Animal , Fat Emulsions, Intravenous/administration & dosage , Fat Emulsions, Intravenous/pharmacology , Female , Heart Arrest/chemically induced , Humans , Male , RatsABSTRACT
We demonstrate a novel application of (13)C pulsed field gradient (PFG) NMR to monitor mass transfer, due to both flow and diffusion, in a 3D complex porous support structure modified by biofilm growth. This enables timescales an order of magnitude larger than previously possible to be accessed with respect to displacement probability distribution (propagator) measurements. The evolution in the propagator shape with observation time to the Gaussian asymptote (constant dispersion coefficient) is consequently well resolved. We also simulated the measured displacement propagators with good agreement between experiment and prediction. The methodology has significant potential for the selective characterization of the transport of nutrients, metabolic products, pollutants and biocides in such complex biofilm-containing structures.
