Editorial ·Editorial comments · waves were first used for kidney stone fragmentation in 1980....

Extracorporeal shockwaves in musculoskeletalsystem (Orthotripsy) is gaining fast and steadyrecognition worldwide because of consistentand good clinical results either with controlledor non-controlled studies on proximal plantarfasciitis of the heel, lateral epicondylitis of theelbow, calcifying tendonitis of the shoulder andnon-union of long bone fracture.

In the past, many physicians remainedskeptical in attitude toward orthotripsybecause of lack of basic scientificdocumentations despite good clinical data andfew sporadic animal experiments. Now, thingshad changed dramatically. The results of manybasic researches had demonstrated thatshockwave application produced biologicalresponses at the tissue level including theinduction of neovascularization associated withincreased expressions of angiogenic growthfactors (eNOS, VEGF, PCNA and BMP etc).The discovery had changed the concept ofshockwave from pure physical and mechanicalimplications to biological mechanism.Therefore, in musculoskeletal tissues,shockwaves manifested themselves asbiological mechanotransduction which differsfrom shockwaves in urology (Orthotripsy). Thepreliminary results of other recent studies inanimal models also showed that high-energyshockwaves might be associated with therelease of NO free radicals and cell apoptosisby altering Wnt and DKK-1 molecules at thesub-cellular level. Based on this new concept,many new indications of shockwaves otherthan musculoskeletal disorders had beenreported including but not limited to chronicskin lesions, osteonecrosis of the femoral head,stable angina pectoris, second degree burn,plastic flap reconstruction and antibacterialapplication etc. These new indications hadwidely opened up the field of shockwave inclinical application.

Currently, there are many unsettled issues thatISMST must play a role to resolve them.

1. Many shockwave devices are manufacturedwith different mechanical principles includingelectrohydraulic, electromagnetic andpiezoelectric. Each device recommended itsown energy levels and the numbers oftreatment, and the information are not inter-exchangeable in mathematical and physicalmodels.

2. There has been no clear definition on “high-energy” and “low-energy” shockwaves basedon scientific data.

3. There is no study documenting the dose-response effect of shockwave despite the factthat the time- and dose-dependent effects ofshockwaves were observed in clinical application.

4. It was speculated that NO free radicals mightbe involved in the signal transduction andmediation of physical shockwave at the sub-cellular level. Obviously, further studies areneeded including genome micro-array analysisto validate the actual biological mechanism ofshockwaves in musculoskeletal tissues.

5. In clinical application, shockwave should berecommended as one of the initial choices oftreatment for acute and chronic insertionaltendinopathies rather than only for chronicrefractory conditions of 6 months or longerduration.

6. Furthermore, the off-label indications ofFDA guidelines such as osteonecrosis of thefemoral head, knee and ankle, OCD of the kneeand ankle, infrapatellar tendonitis (jumperknee), chronic skin ulcers, non-union of longbone fracture and stress fracture etc should berecommended as routine practice.

7. The last and the most important issue is thatshockwave should be regarded as a surgicalprocedure since shockwaves cured mostdiseases with one single treatment.Unfortunately, many third party insurancesregarded shockwave as a therapy modality andreimbursed the cost of treatment unfavorably.Therefore, the term of “Shockwave therapy” tobe changed to “Shockwave biosurgery” similarto other procedures such as radiosurgery. Thischange may assist the insurance companies toproperly reimburse the cost of shockwavetreatment.

Under the leaderships and the guidelines ofISMST, we together have made significantimprovement in the field of musculoskeletalshockwaves in the past many years. However,we must work harder and closer together tofurther strengthen the biological concept andthe clinical implication of shockwaves to ourpeers, and make this new effective and safe,non-invasive and non-surgical device availableto patients in need worldwide.

Editorial · Editorial comments

Editorial comments ............................................. 1Physics and technology of shock waveand pressure wave therapy ............................... 2Extracorporeal Shock WaveTherapy (ESWT) in Skin Lesions...................... 13

Instructions for Authors ................................... 15

Inside this Issue

Chief EditorChief Editor• Paulo Roberto Dias dos Santos, MD

(Brazil) - [email protected]

Associate Editor• Ching-Jen Wang, MD (Taiwan)

[email protected]

Editorial Board• Ana Claudia Souza, MD (Brazil)

[email protected]• Carlos Leal, MD (Columbia)

[email protected]• Heinz Kuderna, MD (Áustria)

[email protected]• Kimberly Eickmeier, MD (USA)

[email protected]• Leonardo Jaime Guiloff Waissbluth,

MD (Chile) - [email protected]• Lowel Weil Jr, MD (USA)

[email protected]• Ludger Gerdsmeyer, MD (Germany)

[email protected]• Matthias Buch, MD (Germany)

[email protected]• Paulo Roberto Rockett, MD (Brazil)

[email protected]• Richard Levitt, MD (USA)

[email protected]• Richard Thiele, MD (Germany)

[email protected]• Robert Gordon, MD (Canada)

[email protected]• Sergio Russo, MD (Italy)

[email protected]• Vinzenz Auersperg, MD (Áustria)

[email protected]• Wolfgang Schaden, MD (Austria)

[email protected]

Veterinary Committee • Scott Mc Clure, DVM (USA)

[email protected]• Ana Liz Garcia Alves, DVM (Brazil)

[email protected]• Ana Cristina Bassit, DVM (Brazil)

[email protected]

Editorial Office Avenida Pacaembu,1024CEP 01234-000 - São Paulo - Brazil Fone: 55-11-3825·8699E mail : [email protected]

website: www.ismst.com

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Ching-Jen Wang, M.D.

Clinical professorChang Gung University School of MedicineChang Gung Memorial Hospital - KaohsiungMedical Center · Kaohsiung, Taiwan.

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ZusammenfassungExtrakorporal erzeugte Stosswellen

wurden erstmals 1980 zurZertrümmerung von Nierensteineneingesetzt und sind seitdem zurMethode der Wahl bei den meistenSteinen in Niere und Harntraktgeworden. Neben der Anwendung inder Lithotripsie werden Stosswellenseit den 90er Jahren zunehmend füreine Reihe von Indikationen immusculoskeletalen Bereich mit Erfolgangewendet. Stosswellen sind eineForm mechanischer Energie, die ohneVerletzung der Körperoberflächedurch die Haut in den Körpereingeleitet und in vorherbestimmtenTiefen zur Wirkung gebracht werdenkann. Erzeugt werden Stosswellen inder Medizin durchelektrohydraulische, piezoelektrischeoder elektromagnetische Verfahren.Die mechanischen Wellen werden mitakustischen Linsen oder Reflektorenfokussiert und mit Hilfe vonbildgebenden Verfahren aufZielgebiete im Körper gerichtet. ZurCharakterisierung derStosswellenfelder werden dieParameter Druck, Energie,Energieflussdichte und verschiedenenDefinitionen für die Fokus- undBehandlungszone verwendet. Nebender mechanischen Kraftentfaltung anakustischen Grenzflächen wird auchim Gewebe Kavitation erzeugt, diesekundär zu nadelstichartigenBelastungen von Grenzflächen führt.Auf Grund dieser Krafteinwirkungensind einerseits Fragmentationseffektean spröden Materialien (Nierensteineetc.) oder auch stimulierende Effektewie Erzeugung von Aktionspotenzialenan Nervenzellen und biologischeReaktionen durch Freisetzungverschiedener Stoffe zu verzeichnen.Obwohl speziell die biologischenWirkungsmechanismen weitgehendunbekannt sind, wird dieStosswellentherapie erfolgreich zur

Steigerung der Blutversorgung undvon Stoffwechselprozessen eingesetzt.Letztendlich werden dadurchbiologische Prozesse angeregt, die zueiner dauerhaften Heilung führen.

SummaryExtracorporeally generated shock

waves were first used for kidney stonefragmentation in 1980. They becamethe method of choice for most kidneyand ureteral stones. More than 10years later, shock waves weresuccessfully utilized for the treatmentof several musculoskeletal diseases.Shock waves are mechanical wavespassing through the surface of a bodywithout injury and may acttherapeutically in predetermined areaswithin the body.

Shock wave generation makes useof three different principles:electrohydraulic, piezoelectric andelectromagnetic. They are focusedusing spherical arrangements,acoustical lenses or reflectors. Fortargeting distant treatment areaswithin the body, ultrasound or X-raylocalization devices are used.Important parameters are pressure,energy, energy flux density anddifferent definitions for focal andtreatment areas. Besides mechanicaleffects on acoustic interfaces,cavitation bubbles are generatedwhich, in turn, cause needle-likepunctures at interfaces. Due to botheffects, fragmentation of brittlematerial such as kidney stones andstimulating effects such as thegeneration of action potentials ofnerve cells take place. Biologicalreactions of liberation of differentagents are reported. Shock waves aresuccessfully applied to increase localblood circulation and metabolism,although the biological workingmechanism is still not completelyknown. Final healing is considered dueto these effects.

IntroductionFor the first time in February 1980

kidney stones were successfullyfragmented in the body of a patientusing externally applied shock waves.The mechanical energy of the shockwave was able to be transmitted to thebody and brought into effect on thestone without significant damage tothe tissue. The granular fragmentswere flushed out of the body in anatural way, eliminating the need foran invasive operation, which had beenusual up to that time. This date marksthe beginning of a new eracharacterised by the targetedapplication of therapeutically effectiveacoustic energies in human tissue. Thespecial feature of this new form ofenergy in the medical field is thepossibility of generating the energyoutside of the body and bringing it intoeffect on target areas deep inside thebody without damaging thesurrounding tissue. A new form ofenergy is thus available in addition tothe known forms of ionising radiationfor a multitude of medical applications.

At the end of the 1960s, the ideaarose to generate shock waves in orderto fragment body concrements such askidney stones and gallstones fromoutside without contact. Theprocedure was developed by theDornier Company in Germany in the1970s. With the first successfullithotripsy in a human being1,2,3 thisbecame the method of choice foralmost all kidney stones and stones indifferent areas of the ureter.

After the successful fragmentationof kidney stones, the procedure wasextended with varying degrees ofsuccess to stones in the gallbladder4, inthe common bile duct5, in thepancreas6 as well as in the salivaryducts7,8,9.

The idea of using shock waves todissolve calcium deposits in theshoulder10 or in the areas at which thetendons are attached11 arose. Althoughexperts could not expect a directfragmentation effect due to the mostlysoft consistency of the calciumdeposits compared to hard and brittlekidney stones, surprisingly thetreatments were frequently successful.This demonstrated a new effect ofshock waves on living tissue, namelythe initiation of healing processes dueto improved metabolism and increasedlocal circulation. Today, shock wavesare used to treat pseudoarthrosis12,13,and even in cardiology to treat angina

Physics and technology of shock waveand pressure wave therapy

Othmar WessPhysicistDirector Product Development / MarketingSTORZ MEDICAL AG

pectoris14. There are alreadyindications for further areas ofapplication, so that the potential ofshock waves in medicine seems to befar from exhausted.

In order to prevent reflectionlosses during the transition into thebody, the shock wave must not begenerated in air but in a medium withsimilar acoustic properties as those ofhuman tissue. Generating shockwaves in a water bath that is broughtinto contact with the patient's skindirectly or via a coupling diaphragmis a good solution.

What are shock waves?Shock waves appear in the

atmosphere when explosive eventsoccur, such as when explosive materialis detonated, lightning strikes or whenairplanes break the sound barrier.Shock waves are acoustic waves thatare characterised by high pressureamplitudes and an abrupt increase inpressure in comparison to the ambientpressure. In the atmosphere, shockwaves can be heard directly as loud“bangs”. They can transmit energyfrom the place of generation to distantareas and may cause window panes toshatter, for example.

Despite their relationship toultrasound, shock waves basicallydiffer by having especially largepressure amplitudes. For this reason,steepening effects due to non-linearities in the propagation medium(water, human tissue) have to betaken into consideration. In addition,ultrasound usually consists of periodicoscillations with a limited bandwidth,whereas shock waves are representedby a single, mainly positive pressurepulse that is followed bycomparatively small tensile wavecomponents. Such a pulse containsfrequencies from several kilohertz tomore than 10 megahertz. (Fig. 1, 2)

Mechanisms forgenerating shock wavesElectrohydraulic shockwave generation

The method initially developed byDornier is similar to a lightning strike.A high-energy electrical dischargeacross a spark gap is ignited in awater bath. (Fig. 3, 4, 5)

A capacitor charged with approx.20 kilovolts (kV) is connected withtwo metal electrodes arranged at adistance of approx. 1 mm via a fasthigh-voltage switch. A thin currentpath, a so called leader, firstdevelops, which connects the twoelectrodes with each other. (Fig. 6)

The formation of the leadersrequires some time, during which apath with increased conductivityspreads from one electrode to theopposite one. A bundle of differentleaders is formed, similar to thegrowth of a plant with several shoots.As soon as one branch of the bundlereaches the electrode on the oppositeside, the conductivity between theelectrodes is established. Anincreasing avalanche of currentrapidly heats up this current channel.A hot plasma forms, whichexplosively expands at supersonicspeed over the first millimetres andstrongly compresses the surroundingliquid. Pressure peaks of more than100 megapascals (MPa) = 1000 barare generated within a fewnanoseconds.

The pressure disturbance spreadsradially around the spark as aspherical, divergent wave into thesurroundings and thereby rapidlyloses intensity. After a fewmillimetres, the pressures havesubsided to the point that a regularpropagation takes place withouttaking significant non-linearities intoaccount.

For many indications, such as e.g.the fragmentation of kidney stones,an effect deep within the body, awayfrom the originating point, is desired.To this end, the shock waves arefocused with an ellipsoid-shapedreflector, in the first focal point ofwhich the underwater spark gap isgenerated. A correspondingarrangement was already proposed by

Time/pressure profile of a shock wave. The rise to peakpressure (p+) takes place in a few nanoseconds (ns).The peak pressures reaches values of approx. 10-150megapascals (MPa). The pulse lasts approx. 0.3-0.5µs. The relatively low tensile wave component (p-),which is limited to approx. 10% of the peak pressure,is characteristic.

Fig. 1

Fig. 2

In comparison to shock waves, ultrasound isrepresented by a periodic oscillation of a limitedduration.

Electrode/tip configuration for generatingelectrohydraulic shock waves through underwaterspark discharge.

Fig. 3

High-speed recording of a spark discharge (Frame rate:2 x 105 frames per second). The spark ignition takesplace in frame 2 of the upper row. A plasma bubblesubsequently forms. A shock wave cannot be detectedyet. It has already detached itself between the secondframe of the first row and the second frame of thesecond row.

Fig. 4

High-speed recording of a spark discharge (Framerate: 107 frames per second). The frame rate magnifiedby a factor of 50 shows the propagation of thespherical shock wave around the spark. The shockwave has already separated itself from the plasmabubble in the centre. The plasma bubble continues togrow independently of the shock wave for approx.1-2 milliseconds.

Fig. 5

Fig. 6

Before the actual ignition of the spark, so-called“leaders” form, which create a conductive connectionbetween the electrodes. When one of these leaders hascreated a bridge to the opposite electrode, the currentchannel can expand explosively by discharging thestored energy. (Frame rate: 107 frames per second)

4 5

Frank Rieber in 1947 to treat biologicaltissue. (Fig. 7)

A considerable part of the primaryspherical wave is directed outside ofthe reflector into the second focus ofthe semi-ellipsoid by the reflection onthe reflector surface. The shock wavepressure can be increased to values ofseveral ten megapascals in the vicinityof the second focus and used fortherapeutic purposes such as lithotripsy.Focusing makes it possible to locallylimit the treatment area and preventside effects to a large extent. (Fig. 8)

A disadvantage of generating shockwaves with underwater spark gaps isthat the sparkover and thus thelocation of the shock wave creationvaries spatially due to stochasticfluctuations. After a few thousandshock wave pulses, the electrodes haveto be replaced with new ones. Theelectrode spacing is increased beyonda critical limit by the wear of theelectrodes, which prevents a sparkover. Even before this occurs, thelocation of the spark over can nolonger be precisely controlled. Anexample of an irregular spark over(misfire) is shown in Fig. 9. As aconsequence, considerable pressurefluctuations can be observed in thefocus zone from shock to shock(Fig. 10). For this reason, pressurevalues given for electrohydraulic

generators are always averaged overseveral shock waves, from which thecurrent individual values canconsiderably deviate.

To make matters worse,electrohydraulically generated shockwaves cannot be controlled so well andare sometimes perceived as verypainful and loud, especially at the lowpressure settings that are frequentlyrequired for orthopaedic applications.The reason for this is that the plasmabubble expands up to severalcentimetres. After the shock wave hasdetached itself from the plasmabubble, the bubble grows to a volumeof several cubic centimetres within1-2 milliseconds. The expansion of thebubble comes to a stop and is followedby a rapid collapse after approx. 3milliseconds. The whole process isperceived as an explosive sound butdoes not contribute to the actualshock wave, since this has alreadymoved approx. 1 metre away. Thechronological process of theelectrohydraulic shock wavegeneration is shown in Fig. 11, 12.

After the overwhelming success ofshock wave lithotripsy for kidneystones, it therefore stood to reason tolook for alternative methods of shockwave generation that did not have the

above mentioned disadvantages of theelectrohydraulic method.

Piezoelectric shock wavegeneration

Electroacoustical transducers areknown from ultrasound technologyexperience a pulse-like displacementusing the piezo effect when a voltagepulse of several kilovolts (kV) isapplied. If a large number ofpiezoelectric elements are arrangedon a spherical shape, they can bedisplaced in the direction of thecentre of the spherical shape bysynchronous excitation. A convergentspherical wave thus spreads out,which increases its pressureamplitude to therapeutically effectivevalues on its way to the centre. Incontrast to the electrohydraulicmethod, one cannot speak of shockwaves in the previously defined senseuntil the area of the focal zone, i.e. inthe centre of the spherical shape. Dueto non-linearities a steepening takesplace forming a shock wave in thephysical sense. (Fig. 13)

Piezoelectric systems have a highaccuracy of repetition and are easy tocontrol even in low energy ranges.Pressures of up to 150 MPa (1500bar) are attained in very small focalspots. Unlike electrohydraulictechnology, it is not necessary tofrequently change electrodes. Despitethe large-area spherical shape, theattainable total energy of the radiatedshock wave can be regarded as ratherlow. In modern systems, thisdisadvantage is partially compensatedby using double layers ofpiezoelectric electroacousticaltransducers.

Electromagnetic shockwave generation

The method of electromagneticshock wave generation is based onthe physical principle ofelectromagnetic induction, as usedfor example in loudspeakers. Thearrangement of coils and membranesis optimized to generate powerful andshort acoustical pulses. Two differentconfigurations can be distinguished:1. the flat coil with focusing throughan acoustical lens and 2. thecylindrical coil with a parabolicreflector.

In the case of the flat coil withfocusing by an acoustical lens, aspirally wound coil that is separatedfrom an electrically conductive metalmembrane by a thin insulation layeris placed on a flat surface. If a shortcurrent pulse flows through the coil,a magnetic field is formed around theindividual windings of the coil. Thisfield penetrates through theinsulation layer into the metalmembrane. Due to the fast currentincrease, eddy currents are inducedin the membrane, which in turncreate a magnetic field that isopposed to the original magneticfield. This yields repellent forces that

abruptly press the membrane fromthe coil into the adjacent water bath.The pressure disturbance created inthis way spreads out as a plane pulsewave into the transmission mediumuntil it is transformed into aconvergent spherical wave by anacoustical lens. (Fig. 14, 15)

This method eliminates the needto replace electrodes as expendablesand is also easy to control, just aswith the piezoelectric method. Theenergy output can be consideredgood. A certain disadvantage can beseen in the fact that the possibilitiesfor focusing with acoustical lensescome up against the technical limitsof the lens material. Therefore, onlyshock wave sources with restricteddiameters and limited aperture anglescan be generated, so that the shockwave energy is induced in the bodythrough relatively small areas of skin.Pain in the coupling area thus cannotbe entirely prevented.

In the case of a cylindricalarrangement of the coil, on theother hand, a divergent cylindricalwave is primarily generated, which istransformed into a convergentspherical wave using a specialrotation paraboloid. Regardless of thetechnical limitations of the lensmaterial, it is possible to designreflectors with large diameters and a

great depth of focus that concentratethe primarily generated pressurewaves on the treatment zone in ahighly efficient way (Fig. 16).The shock wave field of anelectromagnetic cylinder source isshown in Fig. 17.

Due to the large apertures andthe according large aperture angle,the shock wave energy can bedistributed over a large surface areaof the body with little pain and canbe narrowly concentrated on thefocal zone inside the body at thesame time. In addition, this makes iteasily technically possible tointegrate location devices such asultrasound transducers or X-raypaths “in-line” on the axis of theshock wave head, in order to treattarget areas deep in the tissuewith high precision.

In the case of both electromagneticshock wave generators as well aspiezoelectric methods, shockwaves in a physical sense are notgenerated until the focal zone,when the pressure amplitudes havebecome so high that steepeningeffects are activated by non-linearpropagation. The steepening of awave into a shock wave is shownin Fig. 18.

Fig. 7

American patent (Rieber) from 1951. It already showsthe principle of electrohydraulic shock wave generationand the planned application for biological tissue.

Fig. 8

Principle of focusing shock waves using a rotationellipsoid. The primarily divergent spherical shock waveis generated in the first focus F1 and transformedthrough reflection into a convergent spherical wavethat is concentrated in the second focus F2. In additionto the focused wave, part of the primary wave continuesto pass divergently out of the reflector.

Fig. 9High-speed recording of an irregular spark discharge(frame rate: 2 x 105 frames per second). Thepropagation of a bent, hose-shaped plasma bubble canbe recognized. This is caused by a spark that does nottake the direct path between the electrode peaks butattaches to the side of the electrodes. Precise focusingthrough a rotation ellipsoid is no longer guaranteedbecause of the deviation from the spherical geometry.

Fig. 10

Pressure measurement in the second focus of anelectrohydraulic shock wave generator. Due to thestochastic variations in the location at which the sparkignition takes place near the first focus, the shock wavepressure varies in the second focus from shock wave toshock wave.

Fig. 11

The phases of the electrohydraulic shock wave generationare represented on the time axis. After the high voltage isapplied to the electrode peaks, a “leader” that determinesthe path of the spark initially develops with a delay. Assoon as a conductive bridge exists between the peaks, thestored electrical energy flows through the spark andexplosively heats up the path. The bubble only expands atsupersonic speed (approx. 2000 m/s) immediately afterthe ignition. As soon as the propagation of the plasmabubble falls below supersonic speed (approx. 1500 m/s),the shock wave separates from the bubble. The bubblecontinues to expand with reduced speed independently ofthe shock wave and collapses after approx. 3 milliseconds(ms), long after the shock wave has separated.

Fig. 12Expansion of the plasmabubble. After approx. 1ms, the plasma bubblehas attained its greatestexpansion of approx.3 cm and collapses afterapprox. 3 ms. (Sequenceof frames: Beginning 1strow from bottom leftupwards and further2nd and 3rd row frombottom to top) Remnantsof the shock wavereflected on the vesselwalls can still berecognized in the firstframe at the bottom left.

Fig. 13

Piezoelectric shock wave generation. Piezoelectricalelements are arranged on a spherical surface and aresynchronously excited by an electrical pulse to emit apressure wave in the direction of the centre of thespherical surface. The process is self-focusing.

Fig. 14

Electromagnetic shock wave generation, flat coil. Aflatly wound coil is covered with an insulation layerand a conductive membrane and isexcited by anelectric shock. Electromagnetic forces repel themembrane and thereby generate a pressuredisturbance that spreads into the surroundingmedium (water) as a plane wave.

Fig. 15

The plane wave is transformed into a convergentspherical wave using acoustical lenses andconcentrated in the treatment zone.

Fig. 16

Electromagnetic shock wave generation, cylinder coiland paraboloid reflector. A coil is wound around ahollow cylinder and covered with an insulating layerand a conductive membrane. An electric shockgenerates repellent electromagnetic forces thatradiate a cylindrical pressure wave at an angle to thecylinder axis, according to the geometry of thearrangement. The wave is transformed into aconvergent spherical wave through reflection on theparaboloid reflector and is concentrated in thetreatment zone.

Fig. 17

Schlieren photograph of the fronts of successive waveson the way from the reflector to the treatment zone.

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All of the described generationmethods are used in differentequipment designs from variousmanufacturers. In the past few years,however, a trend towardselectromagnetic generation methodshas become apparent, since these notonly eliminate the annoying job ofreplacing electrodes but also allow theapplied shock wave energy to be dosedvery precisely and sensitively.

Propagation of shockwaves (reflection,refraction and scatter)

As acoustical waves, shock wavesrequire a medium for propagation. Inthe case of medically used shockwaves, it is usually water in which theshock waves are generated andbiological tissue in which they arebrought into effect. The pressure istransmitted through the displacementof mass particles, as shown in Fig. 19.

The water bath is important for themedical application of shock wavesbecause the transition to body tissuetakes place without a significant

change in the acoustical impedance.Acoustical interfaces at which theacoustical properties of density (ρ)and sound velocity (c) change producea deviation from the straightpropagation of waves due to familiaroptical phenomena such as refraction,reflection, scatter and diffraction.These effects must be taken intoconsideration when applying shockwaves to human beings, in order toensure that the energy can becomeeffective in the treatment zone. On theother hand, these properties of shockwaves can be used to selectively focusand locally release energy in particularareas of the body. (Fig. 20, 21)

As previously mentioned, thegeneration of shock waves in a waterbath or a tissue-like medium isdecisive for preventing a large part ofthe energy from being lost throughreflection when it is induced into thebody. For this reason, the first devicefor kidney stone fragmentationrequired the patient to be submergedin a water-filled tub. Today's deviceswork with the so-called “dry” coupling,with which the water bath isconnected to the body via a flexiblediaphragm. Regardless of this, it mustbe ensured that no organs that containgas (lungs) or large bone structuresare in front of the actual treatmentarea that shield the target area fromthe shock waves and thus prevent thedesired therapeutic effect.

It must also be assumed that softtissues (skin, fat, muscles, tendons

etc.) are not acoustically homogenousor without interfaces either. However,the differences in the acousticalproperties are considerably less thanfor the transition from water to air andvice versa. In addition to absorptionand reflection, refraction effects occurhere that can lead to deviations fromthe straight propagation of shockwaves in the body that are difficult tocontrol.

Shock wave parameters/measurement ofshock wavesShock wave pressure

Shock waves are mainlycharacterised using measurementswith pressure sensors15. This requires avery small sensor with a high loadcapacity and wide frequency reponse.As shown in Fig. 22, the measurementof a shock wave field consists of amultitude of point measurements atdifferent places in the shock wavefield.

In each measurement, the peakpressure p+ as well as the time profileof it with rise time tr, pulse duration tw,tensile phase p- etc. are measured.Shock waves used in medicine showtypical pressure values of approx.10-100 megapascals (MPa) for thepeak pressure p+. This corresponds to100-1000 times the atmosphericpressure. The rise times tr are veryshort at around <10-100 nanoseconds(ns), depending on the type ofgeneration. The pulse duration tw ofapprox. 0.3-0.5 microseconds (µs) isalso quite short (in comparison to themedical pressure waves describedfurther below). Another characteristicof shock waves is the relatively lowtensile wave component p-, which isaround 10% of the peak pressure p+.

The further parameters of theshock wave field are calculated fromthis data in a rather complicated

procedure. If the peak pressures p+that were measured at variouslocations in the shock wave field areplotted in a three-dimensionalrepresentation (in the axial directionof the shock wave propagation andvertically to this as well), a pressuredistribution like the one shown inFig. 23 results.

Obviously shock wave fields donot have sharp boundaries, but theshape of a mountain with a peak inthe centre and more or less steeplyfalling slopes. One therefore speaks ofa pressure distribution. Differentshock wave devices differ in theshape and height of this pressuredistribution, for example.

-6 dB shock wave focusFor the selective treatment of

locally limited areas in deeper tissuelayers (pseudoarthrosis, femoral headnecroses, kidney stones …), shockwaves are bundled to be able tocorrespondingly limit the desiredeffects. The highest pressure valuesare measured in the compressionzone. If the pressure sensor is movedaway from the centre of compression,the pressure values continuallydecrease. As a result of the physicalcharacteristics, it is not possible todraw a sharp boundary beyond whichpressures abruptly fall to zero. Forthis reason, it is not possible tosharply define the effective zone ofthe shock wave with a fixed spatialcontour either. Physically, the focalzone is defined as the area of a shockwave field in which the measuredpressures are greater or equal to halfof the peak pressure measured at thecentre (Fig. 24).

The area defined in this way isalso called the -6 dB focus ordescribed with the abbreviationFWHM (Full Width at HalfMaximum). This is thus a spatial areain relation to the peak pressure,which, however, does not initiallyprovide any information on theenergy contained therein or thebiological effect.

5 MPa treatment zoneOnly together with energy

information is it possible to give animpression of the area in which theshock wave will unfold its biologicaleffect. In other words: The treatmentarea of a shock wave in the body isnot described by the size of the(-6 dB) focus. It can be larger orsmaller. A further value was thereforedefined that is more closely related tothe treatment zone and is not relatedto relative quantities (relationship tothe peak pressure at the centre) butto an absolute quantity, namely thepressure of 5 MPa (50 bar). The5 MPa focus15 was correspondinglydefined as the spatial zone in whichthe shock wave pressure is greaterthan or equal to 5 MPa. If a certainpressure limit is assumed to exist,below which a shock wave has no oronly minor therapeutic effect, this istaken as a measure and assumed tobe 5 MPa here with certainarbitrariness. Even if this value had tobe corrected in the future accordingto the indication, this definition hasthe advantage that it reflects thechange in the treatment zone withthe selected energy setting.

The different zones and theirchanges according to the selectedenergy levels are schematicallyrepresented in Fig. 25.

In this example, it can be seenthat the -6 dB focal zone does notbecome larger or smaller despitedifferent energy settings. When theenergy increases, however, it can be

assumed that the effective zone ofthe shock waves will increase in size.This is expressed in the increasingsize of the 5 MPa zone.

Energy (E)The energy of the applied shock

wave is an important parameter forpractical applications15. It can beassumed that the shock wave onlyhas an effect on the tissue whencertain energy thresholds areexceeded. In addition to the timecurve of the shock wave p(t) (seeFig. 1), the surface A, in which thepressure can be measured, is alsodecisive. Using the acousticalparameters of the propagationmedium density (ρ) and soundvelocity (c) yields the followingequation for energy:E = A/ρc ∫p(t)dt

A distinction is made as towhether integrating the pressure overtime only records the positivepressure components (E+) or thenegative (tensile) components (Etotal)as well. The total energy is usuallygiven with E (without index). Theacoustical energy of a shock wavepulse is given in millijoules (mJ). As arule, several hundreds or thousandsof shock wave pulses are emitted pertreatment, so that the total emittedenergy is yielded by multiplication bythe number of pulses.

Energy flux density (ED)As previously mentioned the

therapeutic effect of shock waves isaffected by whether the shock waveenergy is distributed over a large areaor concentrated on a narrowtreatment zone. A measure of theenergy concentration is obtained bycalculating the energy per area (E/A):E/A = 1/ρc ∫p(t)dt = ED (energy fluxdensity)

Fig. 18

Schematic representation of the steepening ofa wave front due to non-linearities in thepropagation medium. The wave runs fasterin zones with higher pressure and therebysteepens to form a shock wave front.

Fig. 19

Propagation of a shock wave (schematic) throughdisplacement of particles from the rest position andtheir springing back to rest position. The diminishedpressure component of the wave is caused by particlesthat overshoot.

Fig. 20

Reflection and refraction of shock waves at interfaceswith a different acoustic impedance (density p x soundvelocity c).

Fig. 21

Shock waves are scattered by obstacles such as rib bonesand gas bubbles.

Fig. 22

Shock wave fields are measured with a pressure sensorby recording the chronological pressure curves atdifferent places in the field. All other parameters arecalculated from the pressure values plotted over time.

Fig. 23

Pressure distribution in a plane of the shock wavefield, axially in the direction of the propagation of theshock wave and in a lateral direction to this. The peakvalue p+ measured at the respective location in theshock wave field is plotted.

Fig. 24

Representation of the -6 dB focus (defined by the areaabove half of the peak pressure, 1/2 p+) and the 5 MPatreatment zone (defined by peak pressures p > 5 MPa).

Fig. 25

-6 dB focus in comparison to the 5 MPa treatment zonewith different energy settings: low, medium and high.Despite the different energy contents, the dimensions ofthe (-6 dB) focus remain almost unchanged. The 5 MPatreatment focus increases along with the energy leveland thereby demonstrates the expanded activity areaof the shock waves.

with shock waves, which can beselectively used in localizedd areas,even in deeper tissue layers. Thephysically induced energy can elicitbiological reactions via differentaction mechanisms. Frequently, theseactions initially lead to an improvedlocal circulation and then activaterepair mechanisms as a result. Inaddition to the direct mechanicaleffects in tissue, stimulation effectscan also be detected in the nervoussystem, which may correctpathological reflex patterns and inthe process lead to a lastingrecovery.20

Selective application oflocalizedd shock waves

Technical equipment for shockwave application is supplied withdifferent focal distances, dependingon the penetration depth. Forapplications at a depth of severalcentimetres, the equipment must beequipped with a localization device.An X-ray or ultrasound localization isused, depending on the indication.The treatment area is representedwith one of the imaging methods andbrought into line with the treatmentzone of the shock wave device viacorresponding adjustment. Devicesare offered with very differentlocalization concepts in respect toeffort, convenience, precision andlocalization modality.

If the zones to be treated are lessthen 1-2 cm below the body surface,work can generally be done withoutan integrated localization device. Thetarget area can be identified usingseparate ultrasound or X-ray devicesand indicated by simple markings onthe skin. The shock wave device isplaced on these marking points andthe treatment carried out. Such

devices can be offered at acorrespondingly low price, since alocalization device is a considerablepart of the total expense.

For a carefully targeted shockwave application, all deeper areasrequire an integrated localizationdevice that has a precise spatialrelationship to the actual shock waveapplicator. If the configuration of theshock wave source allows thelocalization device to be centrallyintegrated on the shock wave axis(in-line), one has the advantage ofvery high localization accuracy andeasy-to-interpret spatial relationships.Systems located outside of thetreatment head (off-line) may beoperated with some flexibilityindependent from it. The localizationgeometry, however, is more complexand generally not suited to directlydetect obstacles in the shock wavepath. Fig. 30 shows a shock wavedevice with in-line ultrasoundlocalization and a treatment depth ofup to 15 cm. (Fig. 30)

Generation ofpressure waves

In addition to the above-describedshock waves, also pressure waveswith different features are used inmedicine. Whereas shock wavestypically travel with the propagationspeed of the medium (approx.1500 m/s for soft tissue), pressurewaves are usually generated by thecollision of solid bodies with animpact speed of a few metres persecond, far below the sound velocity.First, a projectile is accelerated, e.g.with compressed air (similarly to anair gun), to a speed of several metresper second and then abruptly sloweddown by hitting an impact body. Theelastically suspended impact body is

brought into immediate contact withthe surface of the patient above thearea to be treated, using ultrasoundcoupling gel if necessary. When theprojectile collides with the impactbody, part of its kinetic energy istransferred to the impact body, whichalso makes a translational movementover a short distance (typically < 1mm) at a speed of around one metreper second (typically < 1 m/s) untilthe coupled tissue or the applicatordecelerates the movement of theimpact body.

The motion of the impact body istransferred to the tissue at the pointof contact, from where it propagatesdivergently as a pressure wave.(Fig. 31a, 31b, 31c)

The time duration of the pressurepulse is determined by thetranslational movement of the impactbody and lasts typically approx. 0.2-2milliseconds in tissue. (Fig. 32)

To simulate the conditions whenthe pressure disturbance is inducedinto the body, the displacement of theimpact plate can be investigatedwhen in contact with water. The timeprofile of the displacement is dampedby the coupled water (displacementapprox. 0.06 mm) and slightly

98

The energy flux density ED is givenin millijoules per square millimetre(mJ/mm2). In the case of energy fluxdensity, one also distinguishesbetween integration over the positivepart of the pressure curve or thenegative part as well15. Without index(EFD), the pressure curve is usuallyconsidered including the negative(tensile) components.

The effect of the focusing on theenergy flux density is schematicallyrepresented in Fig. 26.

The above parameters are usuallysufficient to characterise a shock wavefield well for medical applications.Shock wave devices that work withdifferent generation principles candiffer in relation to the listedparameters. The “quality” of the shockwaves used in the treatment zoneshould be independent of thegeneration principle, however. In otherwords: The measurement of the aboveparameters in the treatment zone doesnot allow any fundamental conclusionsto be drawn about the type ofgeneration. “Electrohydraulicallygenerated shock waves are not betteror worse than piezoelectricallygenerated shock waves”, althoughsecondary parameters such as repeataccuracy, meterability, energy range,operating costs for expendables etc.can naturally differ.

Note that the above parameters areusually measured in water. Due to theinhomogeneities in tissue, however,deviations from the straightpropagation of shock waves lead to aspatial expansion of the focal zones.With increasing depth in the body, thepeak pressure as well as the energyflux density will therefore decreasecompared to a measurement in awater bath.

Physical effects ofshock wavesDirect effect on interfacesShock waves have differentcharacteristics as compared toultrasound. Ultrasound has a high-frequency alternating load on thetissue in the frequency range ofseveral megahertz that leads toheating, tissue tears and cavitation athigh amplitudes. One factor, on whichthe effect of shock waves is based, ison a forwards-directed dynamic effect(in the direction of the shock wavepropagation). A momentum acts atthe interface that can be increasedup to the destruction of kidneystones. (Fig. 27)

Since these dynamic effectsbasically occur at interfaces with ajump in the acoustical resistance buthardly ever in homogenous media(tissue, water), shock waves are theideal means for creating effects indeep tissue without interfering withthe tissue in front of it. However, evenless distinct interfaces within softtissue structures experience a smalldynamic effect from shock waves.Topics of discussion include themechanical destruction of cells,membranes and bone trabeculae16, forexample, as well as the stimulation ofcells through reversible deformation ofthe cell membrane.17 As long as thetreated areas are not on the skinsurface, the focusing also makes itpossible to increase the effectivenessin the treatment area whilesimultaneously reducing side effectsoutside of this area.

This yields very different effects onthe tissue, which on the one hand leadto a primary destruction or irritationor to healing processes through

stimulation, which can be observedwith orthopaedic applications inparticular. As a consequence of shockwave therapy, an increased localcirculation and a more intensemetabolism can usually be observed,to which the resulting healing can beattributed.

Indirect effectCavitation

In addition to the direct dynamiceffect of shock waves on interfaces,so-called cavitation occurs in certainmedia such as water and sometimes intissue as well.18 Cavitation bubblesoccur directly after thepressure/tension alternating load ofthe shock wave has passed themedium. A large number of bubblesgrow until approx. 100 microsecondsafter the wave has passed and thenviolently collapse while emittingsecondary spherical shock waves(Fig. 28).

Near interfaces, cavitation bubblescan no longer collapse without beingdisturbed. The medium flowing backinto the bubble (water, bodily fluid)can no longer flow unhindered, andthe bubble therefore collapsesasymmetrically while developing amicrojet.19 As shown in Fig. 29, thisfluid jet is directed at the interfacewith speeds of several hundred metresper second.

The jets have great energy andpenetration power, so that they notonly erode the hard interfaces ofstones but can also penetrate the wallsof small vessels. This causes microbleeding or membrane perforations.The cavitation is not exclusivelylimited to the focal zone, but isespecially pronounced there.Cavitation is another biologicallyeffective mechanism that is available

Fig. 26

With the same total energy, the energy flux densityincreases with focusing. Reducing the area concentratesthe energy and thus increases the effect of the shockwave.

Fig. 27

Effect of a focused shock wave on a cube-shapedartificial stone with an edge length of 10 mm. (Shockwave occurrence from the right). One can see the stoneheld on a wire, the fragmentation into a few pieces andcavitation bubbles in the shock wave path.

Fig. 28

Cavitation bubbles created by a shock wave runningfrom bottom to top. Directly behind the shock wave, thebubbles are still small. They grow within approx. 30microseconds and then collapse while emitting asecondary (spherical) shock wave (circular rings at thebottom of the frame).

Fig. 29

Cavitation bubbles near obstacles cannot collapse in aspherically symmetrical way, since the obstaclehampers the flow of the fluid. This causes thedevelopment of microjets that hit the interface atseveral hundred metres per second and leads toerosion or punch needle-like holes in vessels ormembranes there (schematic).

Fig. 30

Shock wave device with freely movable treatmenthead (electromagnetic cylinder source) and inlineultrasound localisation for surface application andtarget areas up to 15 cm deep.

Fig. 31a

Phases of pressure waves generated by the impact ofsolid bodies on an impact body. The impact bodytransmits a pressure pulse into the coupled tissue.

Fig. 31b

Fig. 31c

emanate from the application point ofthe impact body and travel radiallyinto the adjacent tissue. The energydensity of the induced pressure wavequickly drops with increasingdistance from the application point

(by the proportion 1/r2), so that thestrongest effect is at the applicationpoint of the application piece. Onedifference between focused shockwaves and unfocused pressure wavesis the fact that focused shock waves

can be directed into deeper tissue,where they develop a therapeuticeffect, with less stress to the skin.Unfocused pressure waves, on theother hand, primarily have an effecton the surface.

1110

distorted. (Note the changed timescale). (Fig. 33)

As a result of its displacement, theimpact body transfers a pressuredisturbance to the coupled tissue,which shows the same time behaviourat the contact point as thedisplacement. The pressure pulsestransferred to the tissue thus haveduration of 0.5 ms and are longer thanwith the above-described shock wavesby a factor of approx. 1000. At approx.0-10 MPa, typical peak pressures withthis method are lower by a factor of >10.

The extremely long pulse durationin comparison to shock waves has adecisive influence on the propagationof pressure waves in tissue. Unlikeshock waves, such pressure wavescannot be focused on narrow tissueareas. In relation to the size of thehuman body, focusing cannot beachieved for physical reasons.

A detailed observation of thecollision process between theprojectile and the impact plate,however, shows a further phenomenonthat can be seen in the jagged shape ofthe curve in Fig. 32 and to a lesserextent in Fig. 33.

The projectile and the impact bodyplaced against the body are normallymade from metal materials. When thetwo metal bodies collide, high-frequencyharmonic oscillations (rod waves) areexcited in the metal bodies. Theseoscillations are superimposed on the"slow" translational movement of theimpact body. (Fig. 34a, 34b, 34c)

The impact of the projectile createsa pressure wave in the impact bodythat runs through the impact body atthe typical propagation speed for themetal (v ≈ 5000 m/s). At the distal endof the impact body, the wave isreflected as a tensile wave and returnsto the collision point with theprojectile. The impact body does notseparate from the projectile until thiswave has passed through the impactbody once in both directions. Asdescribed above, the impact bodybegins its translational movement at aspeed of several metres per second. At

the same time, the rod wave that isreflected as a pressure wave passesthrough the impact body once moreand is reflected at the distal end againas in the first passage. The process isrepeated several times, so that thedescribed wave in the impact body issuperimposed on the “slow”translational movement.

Due to the great differences in theacoustical impedance between themetal impact body and the coupledwater or tissue, a large part of theenergy of these high-frequencyoscillations remains bound in theimpact body. Only a small part of theoscillation energy is also radiated intothe water and can be picked up thereusing the usual hydrophones. This isa damped oscillation, as shown inFig. 35. The pressure amplitudesshow values of up to 10 MPa (typically< 1 MPa) and are thus below thepressure values usually achieved byshock waves by a factor of approx.10 to 100. A steepening due tonon-linearities in biological tissue canthus be disregarded.

However, the energy contained inthe high-frequency harmonicoscillation is several orders ofmagnitude smaller than the energycontent of the aforementioned(low-frequency) pressure pulse. It iswithin the range of diagnosticultrasound. Nevertheless, it cannot beruled out that a certain treatmenteffect is related to this.

The previously described pressurepulse, which is long in comparison toshock waves, is difficult or impossibleto detect with the common pressuresensors used in shock wavetechnology.

Pressure waves as described here

Fig. 32

Displacement of animpact body aftercollision with astriking body in theair. The impactbody is displacedapprox. 0.2millimetres (mm)within a period ofapprox. 0.2milliseconds (ms).

Fig. 33

Displacement of animpact body aftercollision with astriking body inwater. The impactbody is displacedapprox. 0.06 mmwithin a period ofapprox. 0.5milliseconds. (Thetime scale ischanged in relationto figure 11.)

Fig. 34a

The displacement of the impact body is superimposedby a harmonic oscillation (rod waves) in the impactbody. a: The projectile hits the impact body. Thepressure disturbance caused by the impact passes to thedistal end of the impact body and is reflected there as atensile wave, b. After the pressure disturbance haspassed through twice, the tensile wave returns to thecollision point with the projectile at the proximal end ofthe impact body, c. Only then does the impact bodydetach from the projectile and move towards thecoupled tissue at a speed of several metres per second.Part of the energy is already radiated into thesurrounding medium at the distal end (schematicrepresentation).

Fig. 34b

Fig. 34c Fig. 35

Measurement of theradiated harmonicoscillationdisplayedschematically as infigure 34. Note thechanged pressurescale. The dampedoscillation shows apeak pressure of lessthan 0.4 MPa (4bar), which isconsiderably lowerthan that of afocused shock wave.

Shock waves Pressure wavesDifference

(focused) (unfocused)

Focus yes no

Propagation non-linear linear

Steepening yes no

Rise time typically 0.01 µs typically 50 µs approx. 1:1000

Compression pulse duration approx. 0.3 µs approx. 200 - 2000 µs approx. 1:1000

Positive peak pressure 0 - 100 MPa 0 - 10 MPa 10:1 - 100:1

Energy flux density 0 - 3 mJ/mm2 0 - 0.3 mJ/mm2 approx. 10:1

DiscussionShock waves have become an indispensable part of

medicine. They are a means of bringing therapeuticallyeffective energies to locally limited places in the body in anon-invasive way. The fact that shock waves selectivelyeffect acoustical interfaces and pass through homogenouselastic tissue without damage for the most part ismedically important. Tissue damage outside of thetreatment zone is almost completely avoided due to thepossibility of concentrating energy through focusing. Thissignificantly increases the therapeutic effects within thetreatment zone, although moderate side effects(haematomas) cannot be entirely ruled out whenespecially high energies are used, as in lithotripsy.

In addition to the fragmentation effect in stonetreatment, the stimulating effect of shock waves onbiological processes has increasingly become the centre ofinterest in the last few years. Although the mechanism ofaction for this is still unknown to a large extent, shockwaves seem to have a special therapeutic potential here.It appears that the principle of action is so universal that amultitude of very different indications respond positivelyto shock wave therapy. In order to study the mechanismsof action, the shock waves that are used must be preciselycharacterised using the parameters described in the text.This is the only way to determine dosage/effectrelationships and obtain sound knowledge about themechanism of action. However, the fact that the focusedshock waves and unfocused pressure waves, which haveclear physical differences, show a similar effect especiallyin the area of stimulating healing processes suggests thatboth forms of energy do not have a direct mechanicaleffect but intervene in the senso-motoric reflex behaviour.It seems that a reorganisation of pathological reflexpatterns that are anchored in memory due to thestimulating effect of shock and pressure waves cannot beruled out.19 This would open up a previously unknownpotential for further therapeutic areas of application.

Shock and pressure waves not only differ in theirphysical characteristics and the technique used forgenerating them, but also in the order of magnitude of theparameters normally used. The differences between themost important parameters listed here are approx. 1-3orders of magnitude.

Interestingly, the simulation effects and therapeuticmechanisms seem to be similar, despite the physicaldifferences and the resulting different application areas(on the surface and in depth respectively). However, thedescribed pressure waves are not able to fragment hardconcrements such as e.g. kidney stones deeper in thebody (> 1 cm). Nevertheless, unfocused pressure wavesseem to be well suited for orthopaedic indications nearthe surface as well as e.g. trigger point therapy.21

Figure 36 shows a combination device for focusedshock waves and unfocused pressure waves. Dependingon the indication, treatment zones several centimetresdeep in the bodycan be treated ina focused wayand zones nearthe surface canbe treated usingunfocusedpressure waves.

Technical differencesThe technical differences are shown below:

Fig. 36

Combination deviceDUOLITH SD1 for

generating andapplying focused shock

waves and unfocusedpressure waves.

12 13

IntroductionSince 1981 extracorporeal shock waves have been used

very successfully for the disintegration of calcifieddeposits in urology as well as in orthopedics. Due to highefficacy and few side effects, this therapy soon becomesvery popular around the world. Since 1990 (1) shockwaves have also been used for a variety of orthopedicindications. The therapy proved effective for tendoninsertion conditions such as fasciitis plantaris (heel spur)and calcific tendinitis of the shoulder. Shock wave therapyis also widely used for lateral epicondylitis (tennis elbow)as described within previous chapters. Due to the few sideeffects shock waves also gain ground for the treatment ofpseudoarthrosis (non union) and delayed union. Non-invasive and without clinical significant side effects, ESWThas also been used successfully in pilotstudies for the treatment of osteochondritisdissecans (OCD) (2) as well as aseptic bonenecrosis (AVN) (3, 4, 12). In Japan, shockwaves were used successfully in animalexperiements for the treatment of ischemia-induced myocardial dysfunction (5). Evenskin flap survival in rats improved as a resultof shock wave treatment (6).

When treating septic pseudoarthrosis(osteomyelitis), often linked to skin lesions(fistula formation, skin defects,Ö), bonetissue would consolidate and skin defectswould heal particularly fast in many cases.In addition, Gerdesmeyer (7) found in vitrobactericidal effect of shock wave therapy.Encouraged by such findings, a pilot studyon the treatment of skin lesions with ESWTwas conducted.

Material and MethodsTo conduct the study an OrthoWave 180c

from MTS was used. Since most oftensurface defects are involved, the shock wave head wasmodified in that the shock wave would no longer befocussed but be roughly plane to the treatment area. Lowenergy flow densities were used to treat the skin lesions.Depending on the size of the defect, the number ofimpulses varied from a few 100 to several 1,000. Noanesthesia was necessary due to the defocussing and lowenergy of the shock waves. In principle, the treatment wasperformed as an outpatient except for those patientsalready admitted for other reasons. Between September2004 and January 2005, 83 treatments were performed atthe Trauma center Meidling Austria on 81 patients

(2 patients were treated in 2 areas). Mean patient age was61 years. The patient group was made up of 37 womenand 44 men. At the same time, 21 patients (13 women and8 men) were treated at Berlin’s Center for ExtracorporealShock Wave Therapy. The mean age was was slightlyyounger (54 y), The skin pathologies are listed in Table 1.

Since no empiric data were available, treatments werecarried out in weekly intervals, in part in biweekly intervals.After the first treatment, the same wound dressing wasused in principle as before the shock wave therapy. Onlyafter the second or third treatment when wound conditionshad improved, adequate options were indicated.

ResultsTable 2 lists the results by lesion cause:

In the beginning of the treatment, all of the treatedskin lesions were to be considered as infected. Particularlystriking was a lessening of the infection after the firsttreatment because of the shock wave related bactericidaleffect. None of the patients received any antiobiotics.None of the patients experienced any worsening of thewoundconditions. Only one (female) patient dropped outafter the first therapy because she expected herself to fail.Dropouts involved for the most part very old, in partdecriped patients who, after the improvement of theirwound, preferred to avoid the strenuous transportation tothe hospital.

Extracorporeal Shock Wave Therapy(ESWT) in Skin Lesions

W. Schaden

R. Thiele

C. Kölpl

A. Pusch

Causes of skin lesions Number

Posttrauma lesions 44

Postsurgical healing disorders 10

Venous ulcer 25

Arterial ulcer 15

Decubital ulcer 5

Burns 5

Total 104

Causesof skin Number Healed >50% <50% Dropoutlesions

Posttraumalesions 44 (42%) 39 (89%) 1 ( 2%) 4 (9%)

Postoperativehealingdisorders 10 (10%) 10 (100%)

Venous ulcer 25 (24%) 9 (36%) 8 (32%) 6 (24%) 2 ( 8%)

Arterial ulcer 15 (14%) 10 (67%) 2 (13%) 1 (7%) 2 (13%)

Decubitalulcer 5 (5%) 4 (80%) 1 (20%)

Burns 5 (5%) 5 (100%)

Total 104 (100%) 77 (74%) 11 (10%) 7 (7%) 9 (9%)

References

1. Wess, O., Physikalische Grundlagen derextrakorporalen Stosswellentherapie,Journal für Minaeralstoffwechsel,4: 7, 2004.

2. Chaussy, C., Schmiedt, E., Brendel, W.:Extracorporeally induced distruction ofkidney stones by shock waves. Lancet2: 1265, 1980.

3. Chaussy, C., Schmiedt, E., Jocham,D., Brendel, W.,Forssmann, B., Walther,V.: First clinical experiences withextracorporeally induced destructionof kidney stones by shock waves.J. Urol.127:417, 19824.

4. Sauerbruch, T., Delius, M.,Paumgartner, G., Holl, J., Wess, O.,Weber, W., Hepp, W., Brendel, W.:Fragmetation of Gallstones byextracorporeal shock waves. N. Engl. J.Med. 314:818, 1986.

5. Sauerbruch, T., Stern, M. and the studygroup for shockwave lithotripsy ofcommon bile duct stones:Fragmentation of common bile ductstones by extracorporeal shock waves.A new approach to biliary calculi afterfailure of routine endoscopic measures.Gastroenterology 96:146, 1989.

6. Sauerbruch, T., Holl, J., Sackmann, M.,Werner, R., Wotzka, R., Paumgartner,G.: Disintegration of a pancreatic ductstone with extracorporeal shock wavesin a patient with chronic pancreatitis.Endoscopy 19:207, 1987.

7. Iro, H., Nitsche, N., Schneider, T., Ell,C.:Extracorporeal shockwavelithotripsy of salivary gland stones.Lancet II, 115, 1989.

8. Iro, H., Schneider, Th., Nitsche, N., Ell,Ch.: Extrakorporale piezoelektrischeLithotripsie von Speichelsteinen -Erste klinische Erfahrungen HNO38:251, 1990.

9. Kater, W., Rahn, R., Meyer, W.W.,Liermann, D., Wehrmann,T.:Extracorporeal shock wavelithotripsy: New outpatient treatmentconcept for salivary gland stones.Deutsche Zeitschrift für Mund-,Kiefer-, und Gesichts-Chirurgie14:216, 1990.

10. Loew, M., Jurgowski, W., Thomsen, M.Die Wirkung extrakorporalerStosswellen auf die Tendinosis calcareader Schulter. Urologe (A), 34:49, 1995.

11. Dahmen, G.P., Haupt, G., Haist, J.,Loew, M., Rompe, J.D., Schleberger R.Die Extrakorporale Stosswellentherapiein der Orthopädie-Empfehlungen zuIndikationen und Techniken. In:Chaussy, Ch., Eisenberger, F., Jocham,

D.,Wilbert, D. (eds.). Die Stosswelle -Forschung und Klinik. Tübingen:Attempto Verlag, 1995.

12. Valchanov, V. Michailov, P. High energyshock waves in the treatment ofdelayed and non-union of fractures. IntOrthop 15:181, 1991.

13. Schaden, W., Kuderna, H.Extracorporeal Shock Wave Therapy(ESWT) in 37 Patients with Non-Unionor Delayed Osseus Union in DiaphysealFractures. In: Chaussy, C., Eisenberger,F., Jocham, D., Wilbert, D. (eds.) HighEnergy Shock Waves in Medicine.Georg Thieme Verlag, Stuttgart 1997.

14. Gutersohn, A., Caspari, G.,Marlinghaus, E. Autoangiogenesisinduced by Cardiac shock wavetherapy (CSWT) increases myocardialperfusion in endstage CAD patients.Abstract: 70. Jahrestagung derDeutschen Gesellschaft für Kardiologie- Herz und Kreislaufforschung,Mannheim, 15.-17. April 2004.

15. Wess, O., Ueberle, F., Dührssen, R.N.,Hilcken, D., Krauss, W., Reuner, Th.,Schultheiss, R., Staudenraus, I.,Rattner, M., Haaks, W., Granz, B.Working Group TechnicalDevelopments - Consensus Report. In:Chaussy, C., Eisenberger, F., Jocham,D., Wilbert, D. (eds.) High EnergyShock Waves in Medicine. GeorgThieme Verlag, Stuttgart 1997.

16. Delius, M., Draenert, K., Diek, Al.,Draenert, Y. Biological effects of shockwaves: in vivo effect of high energypulses on rabbit bone. Ultrasound Med.Biol. 21:1219, 1995.

17. Forssman, B., Hepp, W.: Stosswellen inder Medizin, Medizin in unserer Zeit4 :10, 1980.

18. Church, C. A theoretical study ofcavitation generated by anextracorporeal shock wave lithotripter.J. Acoust. Soc. Am. 86:215, 1989.

19. Crum, L.A., Cavitation on microjets asa contributary mechanism for renalcalculi disintegration in ESWL. J. Urol.140: 1587, 1988.

20. Wess, O. Hypothesis TowardsAssociative Pain Memory and PainManagement by Shock wave Thereapy.Abstract: Seventh Congress of theInternational Society forMusculoskeletal Shockwave Therapy.Kaohsiung/Taiwan, 1.-4. April, 2004.

21. Gleitz, M., Die Bedeutung der Trigger-Stosswellentherapie in der Behandlungpseudoradikulärer Cervicobrachialgien.Abstracts 53. Jahrestagung derVereinigung Süddeutscher Orthopädene.V., Nr. 328, April 2005.

REPRINT REQUEST ANDCORRESPONDENCE TO:

Dr. Othmar WessPhysicistDirector Product Development/MarketingSTORZ MEDICAL AGUnterseestrasse 47 CH-8574 Kreuzlingen SwitzerlandTel.: +41-71-677 4545Direct +41-71-677 4525Fax +41-71-677 4509e-mail: [email protected]

14 15

Newsletter of ExtracorporealShockwave Therapy is an international,peer-reviewed journal produced byInternational Society for MusculoskeletalShockwave Therapy(ISMST) and is issuedthree times a year.

Newsletter of ExtracorporealShockwave Therapy offers the opportunityto publish original research, clinical studies,review articles, case reports, clinicallessons, abstracts, book reviews,conference reports and communicationsregarding the scientific or medical aspectsshockwave therapy.

Manuscript SubmissionAll manuscripts should be sent to the

Editor: By e-mail: [email protected] disk and mail to:Dr Paulo Roberto Dias dos SantosRua Nathanael Tito Salmon, 233Osasco - São Paulo - BrazilCEP 06016-075 We encourage authors to submit

manuscripts via e-mail. When submitting bye-mail, print mail address and telephoneand fax numbers also should be included.

Manuscript Categories All articles should be well-written in

plain English, whereby jargon, acronyms,abbreviations and complicated data shouldbe avoided. Scientific research:

Theoretical or experimental (basic orapplied) scientific research or the practicalapplication of this research. The articleshould consist of an abstract, key words,introduction, methods, results, discussion,and conclusion.

Length: The manuscript should be nolonger than 2,500 words, including title page,abstract, references, legends and tables.Review articles:

Review articles on topics of generalinterest are welcomed. Reviews shouldinclude the specific question or issue thatis addressed and its importance for theshockwave therapy community, andprovide an evidence-based, balancedreview on this topic. The article shouldinclude a description of how the relevantevidence was identified, assessed forquality, and selected for inclusion;synthesis of the available evidence suchthat the best-quality evidence shouldreceive the greatest emphasis; anddiscussion of controversial aspects andunresolved issues. Meta-analyses also willbe considered as reviews. Authorsinterested in submitting a review manuscriptshould contact the editorial office prior tomanuscript preparation and submission.

Length: Approximately 2,000 to 2,500words and no more than 40 references. Case reports

Authors are encouraged to submitarticles with interesting case reports withrelevant information regarding diagnosisand therapy, unique for shockwavetherapy. The articles should be short,accurate and easy to understand, andshould consist of the following:

- A summary with the clinical relevance;

- An introduction explaining the clinicalproblem;

- A short report of the cases, consistingof history, physical examination, furtherinvestigation, treatment and follow-up.

- A discussion, whereby the clinicalconsequences are described and the mostinteresting aspects of the case report.

Length: Approximately 750 to 1,200words and a maximum of 15 references. Clinical lesson

Authors are invited to give a descriptionand background information ofdevelopments in the field of furtherdiagnostics and clinical tests and methodsthat are relevant to all aspects ofshockwave therapy, training andrehabilitation. It is not necessary toinclude examples of patients, as in casereports. The articles should be up-to-date,short, accurate, and easy to understandand should contain the following:

- A summary with the clinicalrelevance (max. 150 words)

- And introduction with the theme ofthe article

- A description of the used test methodor diagnostic

- A conclusion with the practicalrelevance and practical tips.

Length: Approximately 750 to 1,200words and a maximum of 5 references.National organisationcommunications

National organisations are invited todescribe any aspect of medical care orscience in their country, e.g. the functionof their medical committee, medical careof their players, research that is beingconducted etc.

Approximately 300 to 500 wordsLetters to the editor:

Letters discussing an article that hasbeen published in Journal ofExtracorporeal Shockwave Therapy havethe greatest chance of acceptance if theyare sent in with 2 months of publication.Letters that are approved will be forwardedto the author, who will have 6 weeks torespond. The original letter and the replywill be published simultaneously.

Length: Such letters should not exceed400 words of text and 5 references.Research Letters reporting originalresearch also are welcome and should notexceed 600 words of text and 6 referencesand may include a table or figure.Review of the Literature

Authors are invited to submitsummaries of published article of particularinterest for the shockwave therapycommunity. The opinion of the authorshould be stated following each summary.

Length: Such a review should beapproximately 500 to 700 words. A reviewof three articles simultaneously should beno longer than 1,000 words. Conference reports and Abstracts

Authors are invited to submit reportsof conferences they have attended, and toinclude one to three photographs taken atthe meetings. Please include the namesand highest titles of the persons that canbe identified in the photographs.Summaries of work presented at theconference may be submitted forpublication as well.

Length: 300 to 500 words per report orabstract.

Manuscript PreparationManuscripts should be prepared in

accordance with the Uniform Requirementsfor Manuscripts Submitted to BiomedicalJournals (Vancouver Style).http://www.nlm.nih.gov/bsd/uniform_requirements.html

• If submitting by e-mail, text, tables,and figures should be included in the samefile. Do not submit duplicate copies by mailor fax.

• Articles should be in Microsoft Wordformat.

• Double-space throughout, includingtitle page, abstract, text, acknowledgements,references, figure legends, and tables.

• Do not use abbreviations in the titleor abstract and limit their use in the text.

• Please use Times New Roman, size 12.• On the title page include the full

names, highest academic degrees, andaffiliations of all authors. If an author'saffiliation has changed since the work wasdone, list the new affiliation as well.

• Figures, summary tables and diagramsshould be numbered consecutivelythroughout the paper. Photographs shouldbe clearly labelled.

• References. Number references in theorder they appear in the text; do notalphabetise. In text, tables, and legends,identify references with superscript Arabicnumerals. When listing references, followAMA style and abbreviate names ofjournals according to Index Medicus. Listall authors and/or editors up to 6; if morethan 6, list the first 3 followed by et al.

– Journal: Kibler WB. The role of thescapula in athletic shoulder function. Am JSports Med. 1998;26(2):325-337.

– Book: Perry J. Biomechanics of theshoulder. In: Rowe CR, ed. The shoulder.London: Churchill Livingstone, 1988:1-15.

• Footnotes should be avoided.

Review processContributions will be reviewed by the

editorial board for scientific research,review papers, case reports, clinicallessons, and abstracts. Manuscripts shouldmeet the following criteria: material isoriginal; writing is clear; study methods areappropriate; the data are valid; conclusionsare reasonable and supported by the data;information is important; and topic hasgeneral shockwave therapy interest.

Manuscripts with insufficient priorityor quality for publication are rejectedpromptly. Other manuscripts are sent toexpert consultants for peer review. Peerreviewer identities are kept confidential,but author identities are known byreviewers. The existence of a manuscriptunder review is not revealed to anyoneother than peer reviewers and editorial staff.

Intellectual property• The article must be your own original

work. • If the article contains any photographs,

figures, diagrams, summary tables, graphsor other non-textual elements that are notyour own original work, you must ensurethat you have obtained written permissionfrom the copyright owner to include theirwork in your article for publication inJournal of Extracorporeal ShockwaveTherapy. Permission letters must besubmitted with your article.

Instructions for AuthorsDiscussionBased on the initial encouraging

results of our pilot study, a completelynewl potential of shock wave therapyappears to emerge. The patientsenrolled in our pilot study are reportedas a negative selcted patient groupbecause all cases refused to get anysurgical intervention. Patients willingto get surgery were refered to andshock wave therapy was not offered.The promising outcome after this noninvasive treatment option in chronicwound care justifies to indicate shockwave in those soft tissue condition asdescribed above. For sure furtherstudies have to performed todetermine optimum treatmentparameters. Finally subsequentprospective, randomized controlleddouble-blind studies may demonstratethe efficacy and safety of ESWT intreating skin lesions.

Literature1. Haupt G, Haupt A, Gerety B, Chvapil

M., Enhancement of fracture healingwith extracorporeal shock waves. AUAAnnual Meeting, New Orleans 1990.

2. Thiele R., Marx S., Ludwig J., HerbertChr..Extracorporeal ShockwaveTherapy for Adult Osteochondritisdissecans of the Femoral Condyle andthe Talus. 7th Congress of theInternational Society forMusculoskeletal Shockwave Therapy,Kaohsiung April 1-4, 2004.

3. Ludwig J., Lauber S., Lauber J.,Hotzinger H.. Shockwave treatment offemur necrosis in the adult. Z OrthopIhre Grenzgeb.1999 Jul-Aug; 137(4):Oa2-5.German.

4. Lauber S. High energy extracorporealshockwave therapy in femur headnecrosis.Z Orthop Ihre Grenzgeb.2000Sep-Oct; 138(5):Oa3-4.German.

5. Takahiro N., Hiroaki S., Keiji O.,Toyokazu U. et al., Extracorporeal

cardiac shockwave therapy markedlyameliorates ischemia-inducedmyocardial dysfunction in pigs in vivo,Circulation; Vol.110: pp 3055-3061,2004.

6. Meirer R., Kamelger F.S., Huemer G.M., Wanner S., Piza-Katzer H.,Extracorporeal shock wave mayenhance skin flap survival in ananimal model, British Journal ofPlastic Surgery, V. 58; pp 53-57,2005.

7. Gerdesmeyer L., von Eiff C., Horn C.,Henne M., Roessner M., Diehl P.,Gollwitzer H., Antibacterial effects ofextracorporeal shock waves,Ultrasound in Med. & Biol. Vol. 31, pp115-119, 2005.

8. Wang CJ, Wang FS, Huang CC, YangKD, Weng LH, Huang HY. Treatmentfor osteonecrosis of the femoral head:comparison of extracorporeal shockwaves with core decompression andbone-grafting. J Bone Joint Surg Am.2005 Nov;87(11):2380-7.

Figure 1 shows the forearm of a 94 year old female patient after a para-venously applied infusion and a two septic revisions. An abatinginfection with penicillinresistant staphylococcus aureus wasdiagnosed (positive smear test).Because of a chronic COPD the patientis being treated with cortisone. The patient also suffers from chroniclymphatic leukemia. The fist shock wave treatment was applied on10/13/2004 as an outpatient procedure without anesthetics.

Figure 2 shows the same patient 2 weeks after the firstshock wave treatment. A pre-existing therapy withantibiotics was discontinued and the second shock wavetreatment (again without anesthetics) was applied.

Figure 3 shows the lesion of the same patient after thethird shock wave treatment on 11/10/2004.

Figure 4 shows the healing status 6 weeks after startingthe therapy with altogether 4 shock wave treatments. Intotal, the 4 treatments lasted just about 12 minutes.

Figures

Esta publicação é fornecida como um serviço de Merck Sharp & Dohme aos médicos. Os pontos de vista aqui expressos refletem a experiência e as opiniões dos autores. Antes de prescrever qualquer medicamento eventualmente citado nesta publicação, deveser consultada a Circular aos Médicos (bula) emitida pelo fabricante. The views expressed in this publication are independent of the sponsor. Any product mentioned should be used in accordance with the prescribing information provided by the manufacturer.

x horas,duração da ação1

minutos,início da ação1

2424 2424

MC 078/06 01-2007-ACX-06-BR-078-J

Referência bibliográfica: 1. Malmstrom K, Sapre A, Coughlin H et al. Etoricoxib in acute pain associated with dental surgery: A randomized, double-blind, placebo- and active comparator-controlled dose-ranging study. Clin Ther 2004;26(5):667-679.

Resumo do estudo: estudo com distribuição randômica, de grupos paralelos, que envolveu 398 pacientes com dor moderada a intensa após extração de, pelo menos, dois terceiros molares. Os pacientes receberam uma dose única de 60 mg, 120 mg, 180 mg ou 240 mg de ARCOXIA, 400 mg deibuprofeno e placebo. Os pacientes interromperam dois cronômetros durante o tratamento: quando alcançavam alívio perceptível da dor e quando alcançavam alívio significativo da dor. A intensidade e o alívio da dor foram medidos já 15 minutos após a administração da dose. O início da analgesiaocorreu já 24 minutos após a dose em pelo menos 50% dos pacientes tratados com 120 mg de ARCOXIA e a analgesia persistiu por até 24 horas após a dose em 72% dos pacientes tratados com essa dose; as doses mais altas de ARCOXIA não proporcionaram nenhum efeito clínico adicional.

ARCOXIA (etoricoxibe), MSD. INDICAÇÕES: tratamento agudo e crônico dos sinais e sintomas da osteoartrite e da artrite reumatóide, da gota aguda e da dismenorréia primária; alívio da dor aguda e crônica. CONTRA-INDICAÇÃO: hipersensibilidade a qualquer componente do produto, insuficiênciacardíaca congestiva (NYHA ll-lV), doença cardíaca isquêmica e/ou doença cerebral vascular estabelecida (incluindo pacientes recentemente submetidos à cirurgia de revascularização do miocárdio ou angioplastia). PRECAUÇÕES: Como os riscos cardiovasculares dos inibidores seletivos dacicloxigenase-2 podem aumentar com a dose e a duração da exposição, deve-se usar a menor dose efetiva diária pelo período de tempo mais curto possível. Pacientes com fatores de risco significativos para eventos cardiovasculares (p. ex., hipertensão, hiperlipidemia, diabetes mellitus, tabagismo) oudoença arterial periférica devem ser tratados apenas com o etoricoxibe após criteriosa consideração. ARCOXIA não é recomendado para pacientes com doença renal avançada; se o tratamento for necessário, recomenda-se monitorização rigorosa da função renal desses pacientes. Deve-se ter cautelaao iniciar o tratamento com ARCOXIA em pacientes com desidratação considerável e considerar a possibilidade de retenção hídrica, edema ou hipertensão quando ARCOXIA for utilizado em pacientes com edema, hipertensão ou insuficiência cardíaca preexistentes. Os médicos devem estar cientesde que determinados pacientes, especialmente aqueles com mais de 65 anos de idade, podem desenvolver úlcera(s) no trato gastrintestinal superior, independentemente do tratamento. Em caso de disfunção hepática persistente, ARCOXIA deve ser descontinuado. ARCOXIA deve ser utilizado comcautela por pacientes que já tenham apresentado crises agudas de asma, urticária ou rinite causadas pelo uso de salicilatos ou inibidores não específicos da cicloxigenase. ARCOXIA pode mascarar a febre que constitui um sinal de infecção. Gravidez: categoria de risco C. ARCOXIA só deve ser usadodurante os dois primeiros trimestres da gravidez se o benefício potencial justificar o possível risco para o feto. Não se sabe se ARCOXIA é excretado no leite humano; por isso, quando ARCOXIA for administrado a nutrizes deve-se considerar a importância do medicamento para a mãe ao se decidirentre descontinuar a amamentação ou a medicação. A segurança e a eficácia em pacientes pediátricos não foram estabelecidas e, em geral, não foram observadas diferenças no perfil de segurança e na eficácia do medicamento entre pacientes idosos (65 anos de idade ou mais) e pacientes maisjovens. INTERAÇÕES MEDICAMENTOSAS: Varfarina: a administração de 120 mg de ARCOXIA uma vez ao dia foi associada com aumento no tempo de protrombina de aproximadamente 13% (International Normalized Ratio - INR). Rifampicina: ocorreu redução de cerca de 65% das concentraçõesplasmáticas do etoricoxibe quando este foi administrado com a rifampicina. Metotrexato: doses de 60 mg e 90 mg ao dia de ARCOXIA durante 7 dias não exerceram efeito na concentração plasmática ou na depuração renal de 7,5 mg a 20 mg de metotrexato em doses únicas semanais para otratamento da artrite reumatóide. Em um estudo, a dose de 120 mg de ARCOXIA aumentou a concentração plasmática do metotrexato em 28% e reduziu a depuração renal do metotrexato em 13%; por isso, deve-se monitorar a toxicidade relacionada ao metotrexato quando forem administradasdoses maiores que 90 mg de ARCOXIA ao dia com essa medicação. Inibidores da ECA: relatos sugerem que pode haver diminuição dos efeitos anti-hipertensivos dos inibidores da ECA quando ARCOXIA for administrado com essas medicações. Lítio: relatos sugerem que pode haver aumento dosníveis plasmáticos de lítio quando ARCOXIA for administrado com lítio. Ácido acetilsalicílico em baixas doses: pode ser utilizado concomitantemente a ARCOXIA; este, porém não exerce efeitos sobre as plaquetas e não substitui o ácido acetilsalicílico para profilaxia cardiovascular. Anticoncepcionaisorais: a administração concomitante de ARCOXIA e um contraceptivo oral com etinilestradiol aumentou a concentração plasmática do etinilestradiol em 37% a até 60%. Um aumento na exposição ao etinilestradiol pode aumentar a incidência de eventos adversos associados aos contraceptivosorais. REAÇÕES ADVERSAS: as seguintes experiências adversas relacionadas à medicação foram relatadas (incidência e >1%) em estudos clínicos de 12 semanas sobre osteoartrite, artrite reumatóide ou dor lombar crônica: astenia/fadiga, tontura, edema de membros inferiores, hipertensão,dispepsia, pirose, náuseas, cefaléia e aumento de ALT e AST. O perfil de experiências adversas relatadas nos estudos sobre gota aguda e analgesia aguda foi similar ao relatado nos estudos combinados de osteoartrite, artrite reumatóide e dor lombar crônica. POSOLOGIA: Osteoartrite: 60 mg umavez ao dia. Artrite reumatóide: 90 mg uma vez ao dia. Gota aguda: 120 mg uma vez ao dia (somente durante o período sintomático agudo e por não mais que 8 dias). Dor aguda e dismenorréia primária: 120 mg uma vez ao dia (somente durante o período sintomático agudo). Dor crônica: 60 mguma vez ao dia. (Doses maiores que as recomendadas para cada indicação ou não apresentaram eficácia adicional ou não foram estudadas; portanto, as doses acima são as doses máximas recomendadas.) Insuficiência hepática: em pacientes com insuficiência hepática leve (escore de Child-Pugh5-6), a dose de 60 mg uma vez ao dia não deve ser excedida. Em pacientes com insuficiência hepática moderada (escore de Child-Pugh 7-9), não deve-se exceder a dose de 60 mg em dias alternados. Não há dados clínicos ou farmacocinéticos em pacientes com insuficiência hepática grave (escorede Child-Pugh >9). Insuficiência renal: o tratamento com ARCOXIA não é recomendado para pacientes com doença renal avançada (clearance de creatinina <30 ml/min). Não há necessidade de ajuste posológico para pacientes com insuficiência renal leve/moderada (clearance de creatinina e>30 ml/min). REGISTRO MS: 1.0029.0035. VENDA SOB PRESCRIÇÃO MÉDICA.

Nota: antes de prescrever ARCOXIA, recomendamos a leitura da Circular aos Médicos (bula) completa para informações detalhadas sobre o produto.

* Marca depositada no INPI em 31 de janeiro de 2001por Merck & Co., Inc., Whitehouse Station, NJ, EUA.

+ ARCOXIA 120 mg só deve ser utilizado durante o período sintomático agudo.

www.msdonline.com.br

PODER rápido e prolongado

O início da analgesiacomeçou já aos24 minutos

O efeito analgésicopersistiu por até 24 horas

Em um estudo clínico de odontalgia pós-operatória realizado com ARCOXIA 120 mg1+

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