Psychosocial stress-induced activation of salivary alpha-amylase: an indicator of sympathetic activity?
Female; Humans; Male; Adult; Middle Aged; Social Environment; Predictive Value of Tests; Stress; Biomarkers of Pain; Chromatography; High Pressure Liquid; Kinetics; Circadian Rhythm/physiology; Adrenal Medulla/physiopathology; alpha-Amylase/metabolism; Norepinephrine/metabolism; Psychological/enzymology/physiopathology; Saliva/enzymology; Sympathetic Nervous System/physiopathology
Assessment of sympathoadrenal medullary system (SAM) activity is only possible to date via measurement of catecholamines in blood plasma or via electrophysiological methods. Both ways of measurement are restricted to endocrinological or psychophysiological laboratories, as both require either immediate freezing of blood samples or complex recording devices. Efforts have therefore been undertaken to find a method comparable to salivary cortisol measurements, in which noninvasive samples can be taken at any place and stored at room temperature for sufficient time before later analysis in the laboratory. Salivary alpha-amylase (sAA) is a candidate that may prove useful in this context. We show here that sAA activity is increased by acute psychosocial stress (Trier Social Stress Test) and that increases in sAA correlate with increases in norepinephrine. We further report that sAA exhibits a stable circadian pattern that mirrors that of salivary cortisol. In conclusion, the current data show that salivary alpha-amylase may serve as an easy-to-use index for SAM activity. However, some questions remain to be answered; for example, what impact does salivary flow rate exert on stress-induced sAA activity?
2004
Rohleder N; Nater UM; Wolf JM; Ehlert U; Kirschbaum C
Annals Of The New York Academy Of Sciences
2004
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Journal Article
<a href="http://doi.org/10.1196/annals.1314.033" target="_blank" rel="noreferrer">10.1196/annals.1314.033</a>
Pharmacokinetics of methadone in children and adolescents in the perioperative period
Child; Analgesics; Methadone; Narcotics; adolescent; Opioid; Antitussive Agents; Biological Transport; Kinetics; Perioperative Care; Pharmacokinetics
Introduction Previous studies by Gourlay and coworkers1-3 have demonstrated that in adults undergoing surgery, methadone has slow elimination and a very long duration of effective analgesia. For children, intramuscular injections are a major source of distress in the peri-operative period. If methadone behaves in children as it does for adults, then use of methadone intravenously should provide a steady analgesic effect. For these reasons, we have undertaken studies of methadone in children and adolescents undergoing major surgery. Methods Fifteen children and adolescents, ages 1-18 years were enrolled with informed parental and patient consent according to procedures approved by the institutional Human Studies committee. Enrollment was restricted to patients requiring prolonged surgery (greater than 3 hours) and placement of arterial cannulae or multiple venous cannulae. Included in the studey were 3 one-year olds, 2 two-year olds and 2 three-year olds. Following tracheal intubation and line placement, methadone (0.2 mg/kg) was administered via rapid intravenous bolus. Heparinized plasma samples for methadone assay were obtained at approzimately 1, 2, 3, 4, 7, 10, and 30 minutes and 1, 3, 6, 12, 18, 24, 48, and 72 hours. Methadone assay (gas-liquid chromatography with mass spectrometry) yielded a lower detection limit of 5 ng/ml; for several patients the final 1-4 points fell below the detection limit and were excluded from analysis. Concentration versus time curves were fitted to a bioexponential equation using nonlinear least-squares. Results Kinetic parameters are summarized in Table 1. It is apparent that in children and adolescents ages 1 to 18 years, methadone has very prolonged elimination and a low clearance rate. For this population, regression analysis showed no dependence of half-lives or normalized volumes and clearances on patient age or weight. Areas under the concentration-versus-time curves from the equation parameters and from the trapezoid rule (model-independent) agreed to within 4%. Discussion Methadone has not been studied previously for post-operative pain in children. Observation of the patients in this study and of 16 additional children suggests that methadone provides prolonged analgesia; many children remained comfortable and required no analgesia for 12-36 hours post-operatively. Studies in progress are directed at testing these impressions via double-blinded administration and formal pain assessment scales. If these studies confirm that methadone's dynamics as well as kinetics are similar in children and adults, then peri-operative administration would be a safe, inexpensive and convenient means for providing prolonged analgesia and decreasing the use of painful intramuscular narcotic injections in children following major surgery. In adults ages 29-69 years, there was a positive correlation between age and beta half life. In the present study, we found no dependence of elimination half-life or normalized clearance on age for patients ages 1-18. The mean value for elimination half-life in the present study, 19.2 hours, is indistinguishable from that of the youngest adults in the previous study. As with adults, there is substantial variability among children in the rates and volumes of methadone distribution and elimination. It therefore seems prudent to follow an approach similar to that used in adults with titration to clinical effect. To date, at least 40 children have received methadone (via blinded or unblinded administration) in this fashion without requiring naloxone or assisted ventilation postoperatively. Further study is required before these conclusions can be extrapolated to newborns and very young infants.
1987
Berde CB; Sethna NF; Holzman RS; Reidy P; Gondek EJ
Anesthesiology
1987
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Journal Article
<a href="http://doi.org/10.1097/00000542-198709001-00519" target="_blank" rel="noreferrer">10.1097/00000542-198709001-00519</a>
Morphine kinetics in children
Child; Female; Male; Pain; Analgesia; Preschool; infant; Anesthesia; Human; Adolescence; Operative; Surgical Procedures; Kinetics; Morphine/administration & dosage/blood/metabolism; Preanesthetic Medication
The kinetics of morphine in the plasma of children (0 to 15 yr) can in most cases be adequately described by a triexponential function. When the dosage in children receiving morphine as premedication before surgery is based on kilograms of body weight, there are only minor differences in the kinetic patterns of morphine at different ages (0 to 1, 1 to 7, and 7 to 15 yr). No significant difference in the morphine kinetics was observed between patients (7 to 15 yr) receiving the drug only as premedication and those who also received doses during surgery. The minimum morphine concentration in plasma necessary to suppress the clinical signs of pain during surgery was found to be 65 ng/ml (95% confidence limits of 46 to 83 ng/ml). Based on these minimum effective plasma levels of morphine, there does not seem to be any difference between children of different ages in their sensitivity to morphine. No difference was found in the minimum effective level of morphine when clinical signs of pain were observed by different anesthesiologists.
1979
Dahlstrom B; Bolme P; Feychting H; Noack G; Paalzow L
Clinical Pharmacology & Therapeutics
1979
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Journal Article