Remifentanil-midazolam sedation for paediatric patients receiving mechanical ventilation after cardiac surgery.

BACKGROUND: Sedation of critically ill children requiring artificial ventilation remains a therapeutic challenge due to large individual variation in drug effects and a paucity of knowledge of pharmacokinetics in this population. This study aimed to determine the pharmacokinetics of remifentanil in children requiring ventilation after cardiac surgery. METHODS: Twenty-six ventilated children aged 1 month to 9.25 yr (median 1.77 yr) who had undergone cardiac surgery were sedated with a fixed rate infusion of midazolam 50 microg kg(-1) h(-1) and a remifentanil infusion that was commenced at 0.8 microg kg(-1) min(-1) for a minimum of 60 min and subsequently decreased by 0.1 microg kg(-1) min(-1)every 20 min until the patient awoke. Arterial blood concentrations of remifentanil and midazolam were measured using high-performance liquid chromatography. Mixed-effects population models were fitted to the remifentanil concentration-time data. RESULTS: Satisfactory sedation was achieved in all patients as assessed by Comfort score during the initial maintenance and reduction phase of the remifentanil infusion. One patient was withdrawn from the study due to hypotension. Remifentanil pharmacokinetics were best described using a two-compartment allometric model. For a typical child with a body weight of 10.5 kg, clearance was 68.3 ml kg(-1) min(-1), intercompartmental clearance was 80 ml kg(-1) min(-1), the central compartment volume was 91.7 ml kg(-1), and the peripheral compartment volume was 141 ml kg(-1). CONCLUSIONS: A combination of remifentanil and midazolam provided satisfactory sedation for these patients. Owing to enhanced clearance rates, smaller (younger) children will require higher remifentanil infusion rates than larger (older) children and adults to achieve equivalent blood concentrations.

Quality assurance of ultrasound imaging instruments by monitoring the monitor.

Ultrasound quality assurance (QA) is a means of assuring the constant performance of an ultrasound instrument. A novel 'ultrasound image analyser' has been developed to allow objective, accurate and repeatable measurement of the image displayed on the ultrasound screen, i.e. as seen by the operator. The analyser uses a television camera/framestore combination to digitize and analyse this image. A QA scheme is described along with the procedures necessary to obtain a repeatable measurement of the image so that comparisons with earlier good images can be made. These include repositioning the camera and resetting the video display characteristics. The advantages of using the analyser over other methods are discussed. It is concluded that the analyser has distinct advantages over subjective image assessment methods and will be a valuable addition to current ultrasound QA programmes.

Blood flow measurement by Doppler ultrasound: a question of angles.

Ultrasound Doppler equipment is widely used to estimate blood velocity and volume flow. Recently there has been correspondence concerning the origin of the Doppler shift in blood vessels. The assumption that only the movement of the target need be considered is challenged by the observation that Doppler shifts occur where there is relative motion. In blood there is unlikely to be relative motion between a reflecting blood corpuscle and its supporting plasma. In the simple case of plug flow the relative movement takes place at the vessel wall. An investigation is described which uses a flow rig Doppler phantom to assess what effect, if any, this phenomenon would have on Doppler shift results obtained by insonating a vessel such as the aortic arch and range gating through a curved section where flow velocity gradients are encountered. It has been assumed that if the sample volume were to lie in that part of the vessel in which the blood velocity vector were directly towards the probe, then an angle of 0 degrees could be assumed for calculations using the Doppler equation. Our results indicate that the observed Doppler shifts lie midway between those expected if the shift were to occur solely at the first moving fluid boundary and those originating only from scatterers within the sample volume.

Tandem mass spectrometry of peptides using hybrid and four-sector instruments: a comparative study.

Product-ion spectra produced by high- and low-energy collisionally activated dissociation (CAD) of [M + H]+ ions of a series of peptides (Mr 550-2500) have been compared on four-sector and hybrid tandem mass spectrometers, respectively. The fast atom bombardment product-ion spectra obtained for the smallest peptide analyzed (methionine-enkephalin) were remarkably similar, but substantial differences in fragmentation were observed for the heavier analytes. For peptides with Mr greater than 1000, more complete sequence information was obtained from high-energy CAD on the four-sector instrument. Nevertheless, low-energy CAD on the hybrid mass spectrometer was able to produce partial sequence information even for the largest of the peptides compared. Limits of analysis, defined as the least quantities of analyte for which product-ion spectra of essentially uncompromised quality could be obtained, were similar (ca. 15 pmol) for small peptides, but lower limits were achieved for larger peptides (Mr greater than 1000) with the four-sector instrument. High-energy CAD spectra were found to be highly reproducible, with qualitatively similar spectra obtained over a wide range of operating conditions. In contrast, it was necessary to carefully control collision gas pressures and collision energies in order to obtain good reproducible data for low-energy CAD. Experimental procedures for obtaining reproducible spectra with good sensitivity for peptides on the hybrid instrument are presented.

Preparation and tandem mass spectrometric analyses of deuterium-labeled cysteine-containing leukotrienes.

Leukotrienes (LT) C4, E4 and N-acetyl-E4, their respective monomethyl esters and 14,15-2H2 analogs have been synthesized. The collisionally activated decompositions of the [M + H]+ and [M - H]- ions formed by fast atom bombardment (FAB) have been studied by tandem mass spectrometry using a hybrid sector/quadrupole instrument. Structurally informative product ion spectra were obtained for each analyte; the fragmentation pathways proposed are consistent with the parallel data obtained for labeled and derivatized species. Fragmentation of [M + H]+ ions occurs prominently via cleavage of the thioether linkage with charge retention on the cysteine-containing (predominant for LTC4) or lipid-derived (predominant for LTE4) moieties. More pronounced differences were observed between the fragmentations of [M - H]- ions derived from LTC4 and LTE4; the preference for charge retention, however, parallels that observed for the fragmentation of [M + H]+ ions. Selected ion monitoring during continuous-flow FAB mass spectrometric analysis of authentic LTC4 indicated a low-picogram detection limit.

The fruitfly Drosophila melanogaster contains a novel charged adipokinetic-hormone-family peptide.

A member of the RPCH/AKH (red-pigment-concentrating hormone/adipokinetic hormone) family of arthropod neuropeptides was identified in the fruitfly Drosophila melanogaster, and its structure was determined by automated Edman degradation and m.s. using fast-atom-bombardment ionization and a tandem hybrid instrument capable of high sensitivity. The sequence of this peptide, which we call 'DAKH', is pGlu-Leu-Thr-Phe-Ser-Pro-Asp-Trp-NH2 (where pGlu is pyroglutamic acid and Trp-NH2 is tryptophan carboxyamide). H.p.l.c. analyses of extracts of the three body segments revealed that more than 80% of the peptide is contained in the thorax. Although DAKH is typical of family members in its general structure and distribution in the animal, it is unique in containing a residue which is charged under physiological conditions. The evolutionary significance of this change is considered.

Elucidation of some fragmentations of small peptides using sequential mass spectrometry on a hybrid instrument.

Sequential daughter-ion-scanning analyses of small peptides have been performed using a hybrid tandem instrument of BEqQ configuration. Precursor ions are selected by B and allowed or induced (by high-energy collisional activation) to decompose in the region preceding E. Decoupling of E from the accelerating voltage permits the selection of the first-generation daughter ion whilst retaining appropriate float voltages for the quadrupole assemblies. The daughter ion selected by E is further subjected to low-energy collisional-activation dissociation (CAD) in q and the fragment-ion spectrum is obtained by scanning Q. The sequential daughter-ion-scanning technique has been used to establish that 'internal' fragments of the types, (AY') and (BY'), are formed via initial Y-type cleavage. Fragmentation of a protonated peptide (angiotensin III) by loss of the C-terminal amino acid residue, yielding a (B'n + OH) ion, is reported for the first time. This process is analogous to that previously described for metal-cationized peptides.

Vibrations in orthopedics.

Measurements of various mechanical properties of skeletal material using vibration techniques have been reported. The purposes of such investigations include the monitoring of pathogenic disorders such as osteoporosis, the rate and extent of fracture healing, and the status of internal fixations. Early investigations pioneered the application of conventional vibration measurement equipment to biological systems. The more recent advent of the microcomputer has made available to research groups more sophisticated techniques for data acquisition and analysis. The economical advantages of such equipment has led to the development of portable research instrumentation which lends itself to use in a clinical environment. This review article reports on the developments and progression of the various vibrational techniques and theories as applied to musculoskeletal systems.

Dual metastable peak monitoring: application to the analysis of oestradiol-17 beta as the bis (tert-butyldimethylsilyl) ether.

A new approach to dual metastable peak monitoring has been developed, based on synchronous switching of the accelerating voltage and electric sector voltage of a double-focusing mass spectrometer. The technique has been applied to the determination of oestradiol-17beta as the bis(tert-butyldimethylsilyl) ether, using the 2H3 analogue as internal standard. The detection limit was approximately 5 pg during monitoring of the [M]+ X----[M-C4H9]+ fragmentation. Analyses of plasma extracts indicated that greater selectivity of detection was achieved during metastable peak monitoring than during high resolution (8000) selected ion monitoring of the parent ion.

External quality assessment of assays for cortisol in plasma: use of target data obtained by gas chromatography/mass spectrometry.

We describe procedures for measuring cortisol in plasma and serum by isotope dilution and mass spectrometry. A method that incorporated solvent extraction, derivatization, and gas chromatography/high-resolution mass spectrometry provided data of good precision; interassay CVs were generally 3 to 4% for the concentration range of 100-650 nmol/L. Replacing solvent extraction with extraction on a column of Lipidex 1000 or extraction by immunoadsorption yielded data in excellent agreement with the first method. Plasma and serum pools were analyzed to provide target data for use in the U.K. National External Quality Assessment Scheme for cortisol assays. Routine laboratory assays, as judged by comparison with mass-spectrometric data, were generally positively biased except for analysis of a charcoal-stripped plasma supplemented with cortisol. The results emphasize the importance of using unadulterated plasma or serum pools in assessments of steroid assay procedures.