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T ]T1㣥Y*eO^J,<Getting Started - Setting Your ModelRunning Simulations - Intermittent DosingRunning Simulations - Bolus Dose and InfusionRunning Simulations - Custom dosingRunning Simulations - Constant ConcentrationSaving DataPrinting the graphTest RoutinesFurther Reading11v
3 4About Atracurium ModellerWritten throughout using Borland's Delphi and the Turbo Pascal Programmer's Library. This program is in the public domain.Hardware / software.As this is written in Delphi, Windows 3.1 or later required. 80386 or better, maths co-processor strongly recommended. Memory : this program has run well in 8MB. This program has been written in 640*480*16 resolution ( standard VGA ). A mouse is not essential as all options are available via the keyboard.1 0
WARNING:This program simulates the pharmacokinetics of atracurium within a typical adult patient.This program is intended as an aid to teaching pharmacokinetics to trainee anaesthetists. It is not intended to connect to or control, directly or indirectly, any injection or infusion device or pump. The user of this program is advised to ensure that the protocol used conforms to the current dose and other recommendations as published in the Data Sheet.*
/ ,The author cannot take any responsibility for maladministration of atracurium.This program presumes that the effect of atracurium remains constant. Care should be exercised in any patient who is hypothermic or receiving volatile agents.The author would appreciate that you register the use of this program. There is no fee for registration.Please email : rmuirhead@compuserve.com RMuirh3716@aol.comor telephone ( UK ) 01709 824550 ( ask for / leave message for Dr. Richard Muirhead ).1N
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6 JSetting your model parameters.Three sets of parameters are hard coded :( a ) Default ( Hull ).These parameters are those published in Hull C. J. , British Journal of Anaesthesia, 55, No2, Feb 1983, type A model.}DF& This model has a train-of-four model and can be selected when the default parameters are selected or via the menu bar. The scale toggles between linear ( 0 - 100% ) and logarithmic ( 1 - 100% ).N"EF, (D( b ) Alternate ( Hull ).FG& GThese parameters are those published in Hull C. J. , British Journal of Anaesthesia, 55, No2, Feb 1983, type B model. This model also includes a train-of-four.DFG- *.( c ) Marathe.GI: BThese parameters are those used by Steven Shafer in his excellent STANPUMP program, available from http://www.stanford.edu. The Marathe data set incorporates effect compartment modelling. This model also includes train-of-four.( d ) Custom.There is also a custom parameters setting. There is no train-of-four.This command opens an .INI file ( defaults to WINATRAC.INI ) containing the parameters. Sample INI files are included. There is only one section:-4G,J& [custom]xIJ% There then follows entries for all the constants. All need to be specified, but an entry of 0 ( zero ) is acceptable.j*,J3L@ NUv1Main ( plasma ) compartment in litres.v2Second compartment in litres.V3Effect compartment in litres.doseDose of atracurium in mg ( this setting is overridden in some simulations ).k10k20k12k21k1eke0 Rate constants in min-1Here is a listing of the default INI file:-JM0 .a@[constants]v1 = 4.620000v2 = 3.350000v3 = 0.000462dose = 42.0k10 = 0.08780000k12 = 0.05910000k21 = 0.08160000k20 = 0.00000000k1e = 0.00000740ke0 = 0.0740000013LDM1DMԀMYN@ NRunning Simulations - intermittent dosing.Three basic simulations for intermittent dosing are provided:-( a )Single dose.A single dose of 0.6mg/kg ( 42mg. in a 70kg patient ).( b )Two doses.DM0O& c!A single dose of 0.6mg/kg followed by 0.3mg/kg at one hour. ( A rather bizarre dosing, but demonstrated in Hull C.J., British Journal of Anaesthesia, 55, No2, Feb 1983 ).IYNyO, (:( c )Multiple dosing.|0O&% !A dose of 0.6mg/kg followed by 0.15mg/kg every 15 minutes. ( This equates to approximately 40 mg yO&Mand 10 mg respectively.)(yON% V&Ԁ0 0Y*A graph of your data will be displayed. See also Saving data. 1N17Ԁ<+ $Running Simulations - bolus dose and infusionThe reason for this simulator was to explore the effects of various bolus dose and infusion protocols. The data sheet states that bolus doses of 0.3 - 0.6 mg/kg and infusion rates of 0.3 - 0.6 mg / kg.hr are appropriate. Several buttons ( or menu choices ) simulate this.The user may also stipulate individual bolus dose or infusion protocols. Entering 0 ( zero ) for either the bolus dose or infusion rate will show the effect of an infusion or bolus dose respectively.vE1 2Y*A graph of your data will be displayed. See also Saving data1<1; D?Y*Custom DosingThis simulation combines both the intermittent dosing and bolus infusion modes.The user is asked to enter the initial conditions in the form of a bolus and infusion - again a bolus or infusion of zero is acceptable.If you choose to change the model then you may enter another infusion or bolus at a specified time. In this way, complex dosing routines can be tested.See also Saving data11gK deOSaving DataSee also Printing the graphAfter each simulation, a graph is displayed. You may save this by performing a Windows screen dump but other options are available.Click on File | Save As... This will prompt you to save the data in a variety of formats. The screen can be saved as a bitmap ( PCX or BMP - change the filename extension as appropriate ). You may also save the file in a 2 data formats:-( a )Columnar ASCII.> JThis will save the file as several columns:Time( minutes )Concentration compartment 1Concentration compartment 2.Concentration compartment 3 ( effect compartment, if present ).Train of four ( on all but custom models ).Infusion rate ( for constant concentration model only).A sample file could start:-Minutes conc1 conc2 effect to4 0 9.090909 0.000000 0.000000 100.00 1 7.868208 0.661604 0.602996 60.80Lg> J 2 6.844916 1.183822 1.083190 8.85 3 5.986846 1.591783 1.462292 1.13 4 5.265740 1.906217 1.758247 0.22If your application does not ignore the top line, open the file in NOTEPAD, note down the column headings and delete the top line.( b ) dBase III file. Columns as above.Most spreadsheet and database programs will load or import these files and, in most cases, is the preferred option.I think most users will find this adequate - if not email me for a patch!11~EgݎP nY*Printing the graphSee also Saving dataThere are two methods for printing:-Click on File | Print to print the graph. This uses the current printer resolution and options are available for landscape or portrait mode, the image scaling to fit the paper. This method will scale the graph to fit the printable are on the paper but will include a grid.For better printouts, save the file as a bitmap and load into PAINTBRUSH ( Windows 3.1 ) or PAINT ( Windows 95 ) to enable editing. ]~8 >Alternatively click on Copy to transfer the image to the clipboard - it may then be edited and saved or transferred to other programs via Paste. If you use copy ensure that the paste area is large enough for the graphic - in winݎ~gdows 3.1 paintbrush in 640*480 mode you will need to turn off the toolbar and drawing controls before pasting.1ݎ1% {~U+ $Constant ConcentrationThis option will attempt to run a constant plasma concentration model. To select, enter your target plasma concentration. The graph will demonstrate the calculated concentration.This option presumes that the initial plasma concentration is already at the target ( i.e. that for a 70kg. patient a bolus dose of 11.2mg will distribute in 2.8l to give a concentration of 4mg/l ). The data files will then give the infusion rate required to maintain that plasma concentration. These figures are intended to illustrate the principle of target concentration infusion and are not intended to be used clinically.N1 2:Y*See also Saving data1U1E
F? L}Test RoutinesSee also Mathematics RoutinesVarious routines have been included to illustrate the accuracy of the mathematics. On a theoretical note, no routine exists that can give a perfectly accurate result, but it is possible to get a very close approximation.Routines are shown to calculate e and 1/e by approximate integration using both Euler's technique ( widespread in this type of software ) and the fourth-order Runge-Kutta ( used in all simulations in this program except the test routines ). 3. *Routines also calculate the terminal concentration in a two compartment model using both simultaneous differential equations and the equation:-C = A * e^( -alpha*t) + B * e^( -beta*t)From the above equation the volumes and rate constants can be derived:-v1 = Xd / ( A + B ) { Xd is the initial concentration }k21 = ( A * beta + B * alpha ) / ( A + B )k10 = alpha * beta / k21k12 = alpha + beta - k10 - k21' v2 = v1 * k12 / k21Testing may thus be carried out by calculating the main compartment concentration at time t using both methods.131=%[0t+ &`Further reading.For the model data used:-a:' uHull C. J. A Model for Atracurium. British Journal of Anaesthesia, 55, No2, Feb 1983.( A prize to the first person to find all the errors in this paper! )Marathe P.H., Dwersteg J.F., Pavlin E.G. et al. Effect of thermal injury on the pharmacokinetics of Atracurium in humans. Anaesthesiology 1989; 70; 752-755.t/ ,For the use of numerical methods in pharmacokinetics:-Hull C. J. Pharmacokinetics in Anaesthesia, Butterworth-Heinemann, ISBN 0 7506 1420 X.For the mathematics of simultaneous differential equations and appropriate software solutions:-Press W.H., Flannery B.P., Teukolsky S.A., Vettering W.T.,Numerical Recipes in Pascal - The Art of Scientific Computing.Cambridge University Press.;% ,@ISBN 0-521-37516-9.Y5%$ j( This book is also available in FORTRAN and C ).110Helvclbrdrrclbrdrt$eplmrgcolortb00 cZԉYI
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