Despite its long use in clinical medicine, protamine concentrations and pharmacokinetics in human... more Despite its long use in clinical medicine, protamine concentrations and pharmacokinetics in humans have not been reported. The occasional reoccurrence of anticoagulation after protamine reversal of heparin led us to hypothesize that protamine plasma concentrations decrease rapidly. We developed a method for the measurement of protamine in plasma. Eighteen fit volunteers gave their consent to receive 0.5 mg/kg protamine sulfate administered IV by an infusion pump over 10 min. Heart rate, mean arterial blood pressure, and cardiac output, all measured noninvasively, were recorded and blood samples obtained during and after protamine infusion. Blood plasma was subjected to solid-phase extraction and high-performance liquid chromatography. The administration of protamine was associated with no significant changes in heart rate, mean arterial blood pressure, or cardiac output. Plasma protamine concentrations decreased rapidly, becoming nondetectable within approximately 20 min. Protamine elimination differed significantly between men and women: men had significantly larger areas under the concentration versus time curve. Model-independent pharmacokinetic analysis revealed median (range) values as follows: volume of distribution at steady state, 12.3 (6.9--63.1) L; clearance, 2.2 (1.1--12.1) L/min; and t1/2, 7.4 (5.9--9.3) min. Concentration versus time plots revealed an atypical pattern inconsistent with usual exponential models. The Schwartz-Bayesian criterion identified a one-compartment Michaelis-Menten model and a two-compartment exponential model with irreversible binding as performing better than conventional one- or two-compartmental exponential models; however, performance errors were large with both Michaelis-Menten and exponential models. All models described rapid decreases in protamine blood concentrations. We developed a method for measurement of protamine in human blood. In volunteers, protamine concentrations decreased rapidly after administration. The rapid disappearance of protamine from the circulation, as defined by a median half-life of 7.4 min, could contribute to cases of "heparin rebound" after initial adequate reversal of heparin.
Direct laryngoscopy and observation of endotracheal tube (ETT) passage between the vocal cords re... more Direct laryngoscopy and observation of endotracheal tube (ETT) passage between the vocal cords remain the criterion standard for verifying endotracheal intubation. Detection of end-tidal carbon dioxide (ETCO2) serves as an invaluable adjunct to confirm endotracheal intubation, detect inadvertent esophageal intubation, and monitor for accidental tracheal extubation. Capnography, however, is often unavailable outside the operating suite. A commercially available, disposable, colorimetric ETCO2 detector (FEF, Fenem, Inc., New York, N.Y.), in which color changes using a numerical scale semiquantitatively measure percent carbon dioxide in exhaled gases, has proved effective in confirming endotracheal intubation in adults, but has not been thoroughly investigated in children. We studied 20 otherwise healthy children, aged 6 mo to 8 yr, with simultaneous infrared and colorimetric ETCO2 measurements during elective general anesthesia to evaluate the efficacy of the colorimetric detector. Two hundred of 200 tracheally intubated positive-pressure breaths and 198 of 200 breaths under spontaneous mask ventilation demonstrated a yellow color change (color level 5 or 6), signifying an ETCO2 greater than or equal to 15 mm Hg (2.0 kPa). Repeated-measures analysis of variance revealed no significant differences in infrared ETCO2 values between the two yellow color levels throughout the study period. The associations among color level, infrared ETCO2 determinations, ETT size, and ETT "leak" pressures estimated by Spearman rank correlation analysis were significant only for higher infrared ETCO2 values with higher ETT leak pressures (P less than 0.05). No complications were observed. The Fenem disposable colorimetric ETCO2 detector effectively confirms clinical signs of endotracheal intubation in children when capnography is unavailable.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors Robert J. Elliott Haskayne School of Business Scurfield Hall University of Calgary 2500 Un... more Authors Robert J. Elliott Haskayne School of Business Scurfield Hall University of Calgary 2500 University Drive NW Calgary, Alberta T2N 1N4, Canada relliott@ucalgary.ca Lakhdar Aggoun Department of Mathematics and Statistics College of Science Sultan Qaboos University ...
Abstract Short non-coding RNAs are known to regulate cellular processes including development, he... more Abstract Short non-coding RNAs are known to regulate cellular processes including development, heterochromatin for-mation, and genomic stability in eukaryotes. Given the impact of these processes on cellular identity, a study was undertaken to investigate possible ...
Despite its long use in clinical medicine, protamine concentrations and pharmacokinetics in human... more Despite its long use in clinical medicine, protamine concentrations and pharmacokinetics in humans have not been reported. The occasional reoccurrence of anticoagulation after protamine reversal of heparin led us to hypothesize that protamine plasma concentrations decrease rapidly. We developed a method for the measurement of protamine in plasma. Eighteen fit volunteers gave their consent to receive 0.5 mg/kg protamine sulfate administered IV by an infusion pump over 10 min. Heart rate, mean arterial blood pressure, and cardiac output, all measured noninvasively, were recorded and blood samples obtained during and after protamine infusion. Blood plasma was subjected to solid-phase extraction and high-performance liquid chromatography. The administration of protamine was associated with no significant changes in heart rate, mean arterial blood pressure, or cardiac output. Plasma protamine concentrations decreased rapidly, becoming nondetectable within approximately 20 min. Protamine elimination differed significantly between men and women: men had significantly larger areas under the concentration versus time curve. Model-independent pharmacokinetic analysis revealed median (range) values as follows: volume of distribution at steady state, 12.3 (6.9--63.1) L; clearance, 2.2 (1.1--12.1) L/min; and t1/2, 7.4 (5.9--9.3) min. Concentration versus time plots revealed an atypical pattern inconsistent with usual exponential models. The Schwartz-Bayesian criterion identified a one-compartment Michaelis-Menten model and a two-compartment exponential model with irreversible binding as performing better than conventional one- or two-compartmental exponential models; however, performance errors were large with both Michaelis-Menten and exponential models. All models described rapid decreases in protamine blood concentrations. We developed a method for measurement of protamine in human blood. In volunteers, protamine concentrations decreased rapidly after administration. The rapid disappearance of protamine from the circulation, as defined by a median half-life of 7.4 min, could contribute to cases of "heparin rebound" after initial adequate reversal of heparin.
Direct laryngoscopy and observation of endotracheal tube (ETT) passage between the vocal cords re... more Direct laryngoscopy and observation of endotracheal tube (ETT) passage between the vocal cords remain the criterion standard for verifying endotracheal intubation. Detection of end-tidal carbon dioxide (ETCO2) serves as an invaluable adjunct to confirm endotracheal intubation, detect inadvertent esophageal intubation, and monitor for accidental tracheal extubation. Capnography, however, is often unavailable outside the operating suite. A commercially available, disposable, colorimetric ETCO2 detector (FEF, Fenem, Inc., New York, N.Y.), in which color changes using a numerical scale semiquantitatively measure percent carbon dioxide in exhaled gases, has proved effective in confirming endotracheal intubation in adults, but has not been thoroughly investigated in children. We studied 20 otherwise healthy children, aged 6 mo to 8 yr, with simultaneous infrared and colorimetric ETCO2 measurements during elective general anesthesia to evaluate the efficacy of the colorimetric detector. Two hundred of 200 tracheally intubated positive-pressure breaths and 198 of 200 breaths under spontaneous mask ventilation demonstrated a yellow color change (color level 5 or 6), signifying an ETCO2 greater than or equal to 15 mm Hg (2.0 kPa). Repeated-measures analysis of variance revealed no significant differences in infrared ETCO2 values between the two yellow color levels throughout the study period. The associations among color level, infrared ETCO2 determinations, ETT size, and ETT "leak" pressures estimated by Spearman rank correlation analysis were significant only for higher infrared ETCO2 values with higher ETT leak pressures (P less than 0.05). No complications were observed. The Fenem disposable colorimetric ETCO2 detector effectively confirms clinical signs of endotracheal intubation in children when capnography is unavailable.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors Robert J. Elliott Haskayne School of Business Scurfield Hall University of Calgary 2500 Un... more Authors Robert J. Elliott Haskayne School of Business Scurfield Hall University of Calgary 2500 University Drive NW Calgary, Alberta T2N 1N4, Canada relliott@ucalgary.ca Lakhdar Aggoun Department of Mathematics and Statistics College of Science Sultan Qaboos University ...
Abstract Short non-coding RNAs are known to regulate cellular processes including development, he... more Abstract Short non-coding RNAs are known to regulate cellular processes including development, heterochromatin for-mation, and genomic stability in eukaryotes. Given the impact of these processes on cellular identity, a study was undertaken to investigate possible ...
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