Current
            Managem of
                     ent
            Postoperative
            Pain
                       ...
Pain is an unpleasent
 sensorial and em   otional
experience associated to a
  real or potential tissue
          dam age
...
The goals of effective and
    appropriate pain
  managem are to…
           ent



 Im  prove quality of life for the
pa...
Effe c tive
po s to pe rative pain
manag e me nt has a
humanitarian ro le ,

         But

the re are additio nal
      me...
Effe c tive pain manag e me nt
is no w an inte g ral part o f mo de rn s urg ic al prac tic e




  Postoperative pain man...
Pain Theories.


          • Specificity theory
          • Pattern theory
          • Gate control theory
INJURY




                          GATE
Various factors: physical, emotional, cognitive or behavioural
                 ...
Conditions that Open the Gate

• Physical conditions
      Extent of injury
      Nature of injury

• Emotional states
   ...
Conditions that Open the Gate

• Physical conditions
      Extent of injury
      Nature of injury

• Emotional states
   ...
Co nditio ns that Clo s e the Gate


• Physical
      M edication
      Counterstim ulation (e.g. heat, massage)

• Emotio...
GOOD PAIN…

Acute pain plays a
useful quot;positivequot;
physiological role
                     • Providing a warning
   ...
BAD PAIN….


           S ho rt te rm
ne g ative e ffe c ts o f ac ute pain

 Emo tio nal and phys ic al
s uffe ring fo r...
Pain as a Health Problem
  Characteristic           Acute Pain                  Chronic Pain

Type               Somátic, ...
MOST FREQUENT SCENARIOS



  Pain           Inflam ation
                       m         Inflam ation
                   ...
MOST FREQUENT SCENARIOS




Inflammation   Pain




                      Accute Gout
Pain Treatm Goals
             ent

            Reduce discapacity

            Improve quality of life

            Use s...
Our m frequent problem
     ost              s

  Chronic Musculoskeletal Pain
Our m frequent problem
         ost              s


Postraumatic Pain   Postoperative Pain
Postoperative Pain

• Pain generates em  otional, physiological and psicological
  responses that affect the final recover...
Postoperative Pain


 Adverse Effects

     Respiratory
   Cardiovascular
   Gastrointestinal
       Urinary
   Neuroendoc...
Pain Evaluation

 • Measurem of self evaluation
           ent
       • VAS –Visual Analogue Scale
       • Numeric verbal...
Pain As s e s s me nt
Pain Treatment

• Opioids
            –System ic
            –Subaracnoid
            –Epidural

• Non Opioid Analgesics
 ...
IAS P Po s to p Pain Pro to c o ls




    International Association for the Study of Pain
S c ale Tre atme nt
International Association for the study of Pain




                      ty
                         ...
Opioids




• Obtained from Opium –Poppy flow      er
  (natural)
• Also Synthetic or sem  i-synthetic
• Sem  i-synthetic ...
Opioids

      Natural                  Synthetic
       Morphine                Levorfanol
         Codein
       Papaver...
Opioid Effects

• CNS: Pow  erful analesic action
   – Efective pain control
   – Eliminates em  otional side

• Respirato...
Opioid Effects


• Muscle:
   – Increase of muscle tone, dose dependent




• Cardiovascular
   –   lowm  iocardial depres...
Opioid Effects

• Sphincter contracture
   – Abdom  inal pain
   – Urinary retention

• Nausea & vomit

• Increase of GI s...
Don’Forget…
                       t
•   Patients m have perm
               ust          anent m edical suport
•   Clearl...
No n Opio id
              Analg e s ic s




        NS AID
          S
                               S alic ilat
      ...
Salicilates

 • Sir John Robert Vane
 • 1982 Nobel Prize
 • Effects of Aspirin in Pain
Salicilates
• Ciclooxigenase non reversible
  inhibition , interfering with
  prostaglandin synthesis

• Aspirin is the pr...
Para-Amino- Phenols




• Good pain and fever control
• No anti-inflam atory effects
                m
• No peripheral cic...
NSAIDS
Non Steroidal Pharm  acologic Agents
          that act on Pain
   and Inflam ation Pathw
               m         ...
Inflam ation
              m


Represents the first step in tissue repair,
  when the chem    ical mediators produce
     ...
Pain and Inflam ation Pathw
                 m           ays

                                       Tissue Damage



    ...
NSAID Actions

             M NSAIDs act as non-selective inhibitors
              ost
              of the ciclooxygenase...
NSAID Facts



- M NSAIDs are w
    ost         eak acids,
w a pKa of 3-5
  ith

-They are absorbed w from the
           ...
NSAID Facts


- M NSAIDs are m
   ost                 etabolized in the liver by
oxidation and conjugation to inactive
m e...
NS AID Fac ts



- Ibuprofen and Diclofenac have
short half-lives (2– hours)
                    3

- Coxibs have an avera...
NSAIDS by chemical family


Propionic acids        Heteroaril- Acetic Acids
                          – Tolmentin
   –   I...
NSAIDS Adverse Effects


The widespread use of NSAIDs has m      eant that the
adverse effects of these relatively safe dr...
NSAIDS Adverse GI Effects



        -These effects are dose-dependent

        -In m any cases severe enough to pose
    ...
NSAIDS Adverse GI Effects


-2008 FDA DATA
    - Estimated to result in 103,000 hospitalizations and 16,500 deaths
    per...
NS AIDS Cardio vas c ular Adve rs e Effe c ts
             Ke arne y e t al., BMJ 2006;332:1302–1308

A re c e nt me ta -a...
NSAIDS Cardiovascular Adverse Effects




In patients w such a history, use of NSAIDs w associated w
             ith     ...
NSAIDS Renal Adverse Effects



 Changes in renal haem odynam (blood
                                ics
flow ordinarily ...
NSAIDS Renal Adverse Effects




                      In renal failure
the kidney is trying to m aintain renal perfusion ...
NSAIDS are good,
but m research is needed
     ore
   to im prove safety and
      increase efficacy
Discovery of COX-2

                            Selective inhibition of COX-2
                             results in anti...
Discovery of COX-2


         COX-1 is a constitutively expressed
                       enzym  e
             w a quot;ho...
Discovery of COX-2




            OXICAM and COXIBS
                  S


           Proved Efficacy and Safety

     FDA...
MYOCHRYSINE




 1936
        CORTONE
                           M




 1949
        HYDROCORTONE




 1952
        DECADR...
ARCOXIA
     Etoricoxib
              S O 2 CH3




Cl




      N



          N
              CH3
Etoricoxib world clinical program

Accute Pain                      Chronic Pain
  – Post dental surgery pain       – Oste...
Etoricoxib world clinical program
Phas e I / Pharmac o lo g y: 651 subjects


Phas e II / Clinic al: OA, RA : 4888 patient...
Po s tOp Pain Re s ults
                                                   Max Pain Relief Score
                         ...
PostOp Pain Results

                                        Average Pain Relief Score
                              3.5
P...
Po s tOp Pain Re s ults
                              Ortho pe dic S urg e ry


 • TKR & THR
 • Post Arthroscopy pain
 • A...
PostOp Pain Results
                 3.5

                 3.0

                 2.5
Puntuación ±EE




                  ...
PostOp Pain Results
                   W “
                    as Rescue” edication needed ?
                             ...
Tolerance Profile Vs. Oxicodone
                    Adverse effects results

                                             ...
Etoricoxib Farmacokinetics

                                              Concentration
                                  ...
Eto ric o xib Me tabo lis m

                         Lowinteraction potential




                                       ...
Medication Interaction

   MEDICATION                         EFFECT
Ketoconazol, ASA,
                     No effect
Anti...
S afe ty Pro file
                 Adverse effects


    7.0
           5.9
    6.0                  5.4
    5.0          ...
S afe ty Pro file
                         Adverse Effects

                                                              ...
GI Adve rs e Effe c ts

                                     Patients with gastric ulcers or erosions diagnosed with endos...
Endo s c o py s tudie s c o mparing
                                          Eto ric o xib in OA & RA
                   ...
Cardio vas c ular adve rs e e ffe c ts

                                              Pbo      60 mg    90 mg    Naproxen
...
Us e with c autio n …




Hiperlipidem heavy sm
            ia,      okers         Pregnancy: 6-9 month   Severe renal Ins...
Co ntraindic atio ns
– Specific Hypersensitivity or Allergy

– Gastric Ulcer, GI Bleeding or acido-peptic disease
  histor...
Etoricoxib
 In ac c ute pain

120 m once a day
     g
Etoricoxib
In Rhe umatho id Arthritis

   90 m once a day
       g
Etoricoxib
in Os te o arthro s is

60 m once a day
    g
Etoricoxib
In c hro nic lo w bac k pain

    60 m once a day
        g
Co nc lus io n
                              I us e Eto ric o xib
                                 be c aus e …

– Pow  er...
I’ used Etoricoxib
 ve
   on myself… .
“ the neww
In        orld there
  w be no pain… ”
   ill
           Apc 7,17;21,4
Thanks
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Thanks
!
Thanks
!
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Postoperative Pain Management
Postoperative Pain Management
Postoperative Pain Management
Postoperative Pain Management
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Postoperative Pain Management

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Current concepts in Postoperative Pain Management, by Prof. Dr. Carlos Leal MD - Bosque University Orthopedics, Bogota

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  • 24/05/09<number>
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  • INFLAMACION y DOLOR: principal causa de consulta mdica. ENFERMEDADES REUMATICAS: 2a causa de incapacidad total por enfermedades crnicasEn diferentes grados el DOLOR y la INFLAMACIN tambin estn presentes en otras lesiones msculo esquelticas (traumticas / quirrgicas). Tratamiento actual es INSATISFACTORIO por falta de EFICACIA y/o TOLERABILIDAD.<number>
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  • Celebrex (Celecoxib): Vida media de 11,2 horas. Dosis de 100 a 200 mg / dia o Bid. Comienzo de la accion en 1 hora. Teratogenico. Metabolismo P 450. Quimicamente es una sulfonamida. Dosis equivalentes Vioxx Vs Celebra: 12.5 mg Vs 200. Dosis equipotentes 25 mg Vs 200 mg/bid.el acetaminofen, que a pesar de tener propiedades analgesicas y antipireticas similares a la de la aspirina no tiene propiedades antiinflamatorias importantes por lo que actualmente no se le considera como un AINE.<number>
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  • Porque el dolor
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  • La mayora de los estudios sobre eficacia no han demostrado mayores diferencias entre los AINES. Sin embargo se han notado diferencias substanciales en la eficacia en pacientes individuales ocasionando un exceso de pruebas y errores por parte de los medicos. Si un pte no responde a un AINE administrado a la maxima dosis recomendada, debera ser suspendido e intentarlo nuevamente con otro.
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  • 1936: MYOCHRYSINE (sales de oro) para el tratamiento de la Artritis Reumatoide.1949: MSD desarrolla el primer corticoesteroide (CORTONE). 1952: Desarrollo de HYDROCORTONE , un sucesor ms potente de Cortone.1958: DECADRON (dexametasona).1965: INDOCIN (indometacina), el ms potente antiinflamatorio no esteroide.1978: CLINORIL (sulindac) nuevo AINE con menos efectros colaterales. 1982: DOLOBID (diflunisal) nuevo AINE.1992: Inicia el desarrollo de los COXIBS. 1998: Lanzamiento de VIOXX, el primer inhibidor especfico de la COX-2.2002: Lanzamiento de ARCOXIA, nueva generacin de Coxibs con eficacia superior a AINEs.60
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  • Modelos de analgesia aguda 120 mg una vez al da y dosis nica. Incluyeron hombres y mujeres mayores de 16 y 18 aos, potextraccin de 2 o ms terceros molares.DOLOR MODERADO A SEVERO.Estudios de rango de dosis: 120 mg. Comparado contra placebo e Ibuprofeno 400 mg. N= 398 pacientes.<number>
  • Protocol 039, estudio fase III, Dolor dental POP, Arcoxia 120 mg,Naproxeno 550 mg acetaminofen-codena 600/60.N= 201 pacientes.CONCLUSION:Efecto similar con naproxeno en las primeras 8 horas y superior al acetaminofn/codeina.Arcoxia superior a placebo en todas las mediciones de analgesia, incluyendo el efecto general, inicio, pico, duracin y efecto analgsico.El efecto de Arcoxia se extendio por 24 horas.<number>
  • studios fase III, Dolor POP de remplazo de rodilla y de cadera. Dos fases: I dolor primeras 24 horas y Fase II: das 2 a 7 das.Protocolo 038: n 264 paciente frente a naproxeno 1 gm.CONCLUSION: Eficacia similar al naproxeno en el efecto del primer da.EN fase II (das 2 a 7): Mayor eficacia analgsica frente al naproxeno, menor analgesia complementaria y mejor desempeo en la evaluacin global del dolor realizada por el paciente.Estudio fase III, protocolo 059. Arcoxia 120 frente a naproxeno 1 gm. N= 228 pacientes.Fase 1 del estudio (24 horas). Fase II del estudio (2 a 7 da).CONCLUSION: Arcoxia 120 tuvo un efecto general, incluyendo el inicio, pico y duracin del efecto analgsico superior al placebo. Similar a 1 gm de naproxen.En estudios post-artroscopia subacromial, 30 pacientes recibieron anestesia general. La mitad de los pacientes recibieron Arcoxia 120 mg. El grupo con arcoxia tuvo puntajes mejores en la VAS, requirieron menor rescate postoperatorio con fentanyl, menor requerimiento de acetaminofen mas codeina en el da posterior a la artroscopia.<number>
  • Protocolo 055, fase III, N=225 pacientes.COCNLUSIONES:Arcoxia 120 superior a placebo en todas la mediciones de analgesia, incluyendo el efecto analgsico generalinicio, pico y duracin del efecto analgsico.Al compara con oxicodona/acetaminofn, Arcoxia tiene un efecto superior y mayor duracin del efecto.<number>
  • Estudio 057: Estudio fase III, N= 320 pacientes.CONCLUSIONES:Arcoxia 120 efecto general superior a oxicodona/acetaminofn 10/650Mayor duracin del efecto, efecto analgsico pico similar, efecto analgsico superior.<number>
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  • Absorcin completa independiente de alimentos u otros medicamentos (anticidos, prednisona, etc.). Una comida alta en grasas, reduce la velocidad sin afectar el grado de absorcin. En las pruebas clnicas se administr independiente de los alimentos. La concentracin plasmtica es proporcional a la dosis y es mxima en 1 hora en adultos cuando se administra en ayunas. Cintica lineal.Tmax muy temprana (~1 hora) con Cmax elevada Vida media de eliminacin de 22 horasFarmacocintica similar:Hombres vs. mujeresAncianos vs. jvenes<number>
  • Metabolismo compartido entre varias sub-familias de CYP. No depende de una sola como otros medicamentos.Unin a protenas 91.9%<number>
  • Warfarina: Aumenta 13% el tiempo de protrombina. Rifampicina: Disminuyo 65% C de Arcoxia. Metotrexate: ↑28% C (dosis > 120 mg de Arcoxia). IECAS: AINES disminuyen efecto antihipertensivo. Litio: AINES aumentan los niveles plasmáticos de Litio. Anticonceptivos orales: Arcoxia 120 mg aumentó los niveles de etinilestradiol de 37% al 60% posiblemente al inhibirir con una enzima sulfotransferasa comprometida en la sulfatación de los estrogenos (sangrados vaginales, turgencia mamaria), en preparados con más de 35 mcg de EE y 0.5 a 1 mg de norethindrona. Al pensarse en una terapia de remplazo hormonal, debe tenerse en cuenta este incremento de la concentración estrogénica.<number>
  • Estos efectos secundarios son del programa general (no Medal):Otros efectos secundarios son sabor metlico y aftas bucales, infeccin de vas urinarias,, cuadro similar a la gripe(0.9-2.2%), pirosis (0.3-5.8%), dispepsia (1.7-4.8%), malestar epigstrico (1.3-5.9%, bronquitis, mareo(1.2-2.4%), astenia/fatiga (0.9-1.9%), rash (0.9-2.2%), dolor de espalda (0.6-2%), tos, dolor abdominal (1.3-3%), faringitis y edema de MMIIs (1.3-3.1%). Estreimiento (0.3-2.4%).Descontinuaron Tx por evento adverso: 4.1% placebo, Etoricoxib 60 mg 6.5%, 90 mg 4.8%, 120 mg 5.8%, Naproxeno 1 gm 7.5%Ibuprofeno 2400 mg 8.5%. EA Postcomercializacin:Se ha encontrado:T. Stma Inmunolgico:hipersensibilidad, anafilaxia.T Siquitricos: ansiedad, insomnio, confusin, alucinaciones.T Stma. Nervioso: disgeusia, somnolencia.T. Cardacos: ICC, palpitaciones.T. Vasculares: Crisis Hipertensiva.T. Respiratorios: Broncoespasmo.T. Gastrointestinales: Dolor abdominal, lceras orales, lcera pptica incluyendo perforacin y sangrado (pp/ancianos), vmitos, diarrea.T. Hepatobiliar: hepatitis.T. Piel y tejido subcutneo: angioedema, prurito, rash, S. Stevens-Johnson, Urticaria.T Renales y Urinarios: Nefropata, incluye insuficiencia renal reversible con el retiro.<number>
  • Estos efectos secundarios son del programa general (no Medal):Otros efectos secundarios son sabor metlico y aftas bucales, infeccin de vas urinarias,, cuadro similar a la gripe(0.9-2.2%), pirosis (0.3-5.8%), dispepsia (1.7-4.8%), malestar epigstrico (1.3-5.9%, bronquitis, mareo(1.2-2.4%), astenia/fatiga (0.9-1.9%), rash (0.9-2.2%), dolor de espalda (0.6-2%), tos, dolor abdominal (1.3-3%), faringitis y edema de MMIIs (1.3-3.1%). Estreimiento (0.3-2.4%).Descontinuaron Tx por evento adverso: 4.1% placebo, Etoricoxib 60 mg 6.5%, 90 mg 4.8%, 120 mg 5.8%, Naproxeno 1 gm 7.5%Ibuprofeno 2400 mg 8.5%. EA Postcomercializacin:Se ha encontrado:T. Stma Inmunolgico:hipersensibilidad, anafilaxia.T Siquitricos: ansiedad, insomnio, confusin, alucinaciones.T Stma. Nervioso: disgeusia, somnolencia.T. Cardacos: ICC, palpitaciones.T. Vasculares: Crisis Hipertensiva.T. Respiratorios: Broncoespasmo.T. Gastrointestinales: Dolor abdominal, lceras orales, lcera pptica incluyendo perforacin y sangrado (pp/ancianos), vmitos, diarrea.T. Hepatobiliar: hepatitis.T. Piel y tejido subcutneo: angioedema, prurito, rash, S. Stevens-Johnson, Urticaria.T Renales y Urinarios: Nefropata, incluye insuficiencia renal reversible con el retiro.<number>
  • El programa de seguridad de Arcoxia se dise para mostrar que tiene un perfil de seguridad similar al de los AINES no selectivos pero superior en relacin al TGI. Arcoxia 120 mg produjo un nivel inferior de prdida de sangre oculta en materia fecal frente a Ibuprofeno 800 mg 3 v/das (p<0.001).Se ha demostrado menos EA sobre la mucosa gstrica. Bsicamente estos hallazgos se dan en estudios de indicacin crnica (OA y AR).La poblacin que recibi Arcoxia tena una gran morbilidad y condiciones pre-existentes. Arcoxia tiene un buen perfil de seguridad y tolerabilidad. En comparacin con el placebo tiene una incidencia de EA similar.En los pacientes que recibieron Arcoxia por ms de un ao, se comprob que no existen eventos de aparicin tarda.<number>
  • Una ventaja fundamental de los Coxibs sobre los AINEs convencionales es el menor potencial de producir eventos adversos GI, incluyendo lceras gastroduodenales. Dos estudios multicntricos, aleatorizados, de grupos paralelos, doble ciego, han demostrado que el perfil de seguridad de etoricoxib es significativamente superior a los AINEs convencionales y equivalente al de otros Coxibs.2El primer estudio comparó la incidencia de úlceras gastroduodenales, por endoscopía, en pacientes mujeres y hombres con OA (edad 50 años) o AR (edad 18 años) quienes se trataron durante 12 semanas con etoricoxib (120 mg una vez al día, n=251), naproxeno (500 mg dos veces al día, n=244), o placebo (n=247). El punto final primario fue la incidencia de úlceras de al menos 3 mm en su diámetro mayor. Al final de las 12 semanas, la incidencia acumulada de lceras gastroduodenales fue 7.42% con etoricoxib (p<0.001 vs. naproxeno), 25.27% con naproxeno, y 1.35% con placebo (p=0.002 vs. etoricoxib, p<0.001 vs. naproxeno). Las erosiones gastroduodenales en pacientes tratados con etoricoxib fueron similares a las del grupo placebo (22.7% vs. 23.2%). Las erosiones gastroduodenales estuvieron significativamente aumentadas con naproxeno en comparacin con etoricoxib y placebo (p<0.001 para etoricoxib y placebo vs. naproxeno). Los pacientes tratados con naproxeno utilizaron significativamente ms medicamentos de rescate que los que recibieron placebo (0.93 vs. 0.63) (p=0.004); etoricoxib y placebo (0.83 vs. 0.63) no tuvieron diferencia significativa en esta medida (p=0.057).<number>
  • En teora un inhibidor selectivo de la COX2, puede alterar el equilibrio prostaciclina-tromboxano, favoreciendo la actividad de ese ltimo y la aparicin de eventos trombticos (los coxibs disminuyen la sisntesis de prostaciclina, un potente vasodilatador y antiagregante, sin afectar el tromboxano).Para este anlisis de incluyeron 10 estudios en OR, AR y lumbalgia crnica. Naproxeno menor incidencia de eventos.CONCLUSIONES:No diferencias en la presentacin de edema de Arcoxia frente a placebo o Naproxeno.No diferencias en la incidencia de ICC, edema pulmonar o insuficiencia ventricular izquierda.La incidencia de Hta de Arcoxia es ligeramente superior al placebo y similar a los AINES no selectivos. No hay una relacin dosis respuesta de este efecto, y no aumentaron en magnitud ni frecuencia con el uso prolongado.Cerca del 50% de los pacientes tenan antecedente de HTA y el 59% TA alta al ingreso al estudio. El 50% de estos pacientes requirieron cambio en su tratamiento antiHTA.<number>
  • El riesgo cardiovascular de los “coxibs” es dosis dependiente y relativo al tiempo, por tanto se deben de usar a dosis mínimas efectivas y por el menor tiempo posible en pacientes en riesgo cardiovascular…..En pacientes con insuficiencia heptica leve no debe excederse la dosis de 60 mg/da. En pacientes con insuficiencia heptica moderada, se aumento AUC 16% a dosis de 60 mg interdiaria.La funcin renal se avlo etoricoxib 90 mg, 200 mg celecoxib bid,naproxeno 500 mg bid, con efectos similares en la excresin de sodio. No hay diferencia en la farmacocnintica del etoricoxib en pacientes con IRC en dilisis. El etoricoxib no es dializable. Cualquier condicin que disminuyan la perfusin renal, tienen rieso como en ICC, cirrosis heptica, deshidratacin y dao renal previo.Arcoxia puede elevar 3 veces las transaminasas en el 1%, similar a lo que ocurre con naproxeno y menos con diclofenaco.En el embarazo Arcoxia est contraindicado en el 3 trimestre porque puede producir cierre prematuro del ductus arterioso.Arcoxia no se conoce si se excreta en la leche materna (si en ratas), lo cual dejara dos posibilidades, suspender lactancia no darlo en mujeres lactantes.<number>
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  • Cuatro tipos de modelo de analgesia aguda: Dolor dental, dismenorrea primaria y pop Qx ortopdica. Total pacientes incluidos 1168 pacientes. Se evalo:Efecto analgsico general: alivio total del dolor en 8 horas (TOPAR8, escala de 0 a 32), Suma de la diferencia de la intensidad del dolor en 8 horas SPID 8 escala de -8 a 24, y la Evaluacin global del paciente a las 8 y 24 horas.Inicio del efecto analgsico: tiempo en el que se presenta alivio perceptible del dolor, PID mayor o igual a 1.Efecto analgsico mximo PID mximo (escala de -1 a 3)Duracin del efecto analgsico: Tiempo para uso de medicacin de rescate, % de pates con medicamento de rescate<number>
  • El programa incluy2824 pacientes, de los cuales 1346 recibieron Arcoxia.Estudio 010: Fase IIB, estudio de determinacin de rango de dosis. Parte I: 8 semanas contra placebo. N= 580 pacientes. Parte II: n=432, informacin de seguridad y tolerabilidad. Conclusin dosis 90 mg (120 mg muy ligera ventaja).Duracin total 174 semanas (con 2 extensiones), con desenlaces de eficacia y seguridad: Evaluacin dolor por el pte, evaluacin global de la actividad de la enfermedad por el paciente, evaluacin global de la enfermedad por el MD, Cuestionario de evaluacin de salud de stanford. A partir de la segunda fase se comparo contra diclofenaco 150 mg daConclusiones:La mejora de arcoxia se mantuvo constante durante el perido de 122 semanas (prueba de consistencia).<number>
  • Total pacientes estudiados en esta indicacin, 2476, de los cuales 1336 recibieron Arcoxia.Estudio 010: Fase IIB, estudio de determinacin de rango de dosis. Parte I: 8 semanas contra placebo. N= 580 pacientes. Parte II: n=432, informacin de seguridad y tolerabilidad. Conclusin dosis 90 mg (120 mg muy ligera ventaja).Duracin total 174 semanas (con 2 extensiones), con desenlaces de eficacia y seguridad: Evaluacin dolor por el pte, evaluacin global de la actividad de la enfermedad por el paciente, evaluacin global de la enfermedad por el MD, Cuestionario de evaluacin de salud de stanford. A partir de la segunda fase se comparo contra diclofenaco 150 mg daConclusiones:La mejora de arcoxia se mantuvo constante durante el perido de 122 semanas (prueba de consistencia).<number>
  • Los estudios en patologas crnicas, adems de la eficacia y seguridad, buscan evaluar la persistencia del efecto teraputico en el tiempo.<number>
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  • Transcript of "Postoperative Pain Management"

    1. 1. Current Managem of ent Postoperative Pain Carlos Leal M.D. Director Orthopedic Research Laboratory Director of Knee Surgery & Sports Medicine Fellowship Bosque University Orthopedic Department Bogotá DC, Colombia
    2. 2. Pain is an unpleasent sensorial and em otional experience associated to a real or potential tissue dam age International Association for the study of Pain
    3. 3. The goals of effective and appropriate pain managem are to… ent  Im prove quality of life for the patient  Facilitate rapid recovery and return to full function  Reduce morbidity  Allowearly discharge from hospital
    4. 4. Effe c tive po s to pe rative pain manag e me nt has a humanitarian ro le , But the re are additio nal me dic al and e c o no mic be ne fits fo r rapid re c o ve ry and dis c harg e fro m ho s pital.
    5. 5. Effe c tive pain manag e me nt is no w an inte g ral part o f mo de rn s urg ic al prac tic e Postoperative pain management -m inim izes patient suffering - can reduce m orbidity - facilitates rapid recovery and early discharge from hospital - can reduce hospital costs
    6. 6. Pain Theories. • Specificity theory • Pattern theory • Gate control theory
    7. 7. INJURY GATE Various factors: physical, emotional, cognitive or behavioural open or close the gate PAIN experienced depending on howfar gate open or closed
    8. 8. Conditions that Open the Gate • Physical conditions Extent of injury Nature of injury • Emotional states Anxiety W orry Tension Depression • Cognitive states Focusing on the pain
    9. 9. Conditions that Open the Gate • Physical conditions Extent of injury Nature of injury • Emotional states Anxiety W orry Tension Depression • Cognitive states Focusing on the pain
    10. 10. Co nditio ns that Clo s e the Gate • Physical M edication Counterstim ulation (e.g. heat, massage) • Emotional state Positive em otions (e.g., happiness, optim ) ism Relaxation Rest • Mental state Intense concentration or distraction Involvem and interest in activities ent
    11. 11. GOOD PAIN… Acute pain plays a useful quot;positivequot; physiological role • Providing a warning of tissue dam age • Inducing im obilization m to allow appropriate healing
    12. 12. BAD PAIN…. S ho rt te rm ne g ative e ffe c ts o f ac ute pain  Emo tio nal and phys ic al s uffe ring fo r the patie nt  S le e p dis turbanc e w negative im ith pact on mood and mobilization  Cardio vas c ular s ide e ffe c ts such as hypertension and tachycardia
    13. 13. Pain as a Health Problem Characteristic Acute Pain Chronic Pain Type Somátic, viscera o referred Persistent/ low back pain Source Accute lesion Multifactorial or unknown Onset / Time Sudden / 6 months Slow / > 6 months Physiological High cardiac and respiratory Symilar to accute, but with Responses rate. High bood glucose. adaptation of blood presure, Decreased gastrointestinal heart rate. motion. Nausea. Blood flow redistribution Psicological Fear, anxiety and bad temper Depression, sleep pattern Responses changes, denial. Prognosis Full recovery Likely Full recovery not likely
    14. 14. MOST FREQUENT SCENARIOS Pain Inflam ation m Inflam ation m Pain Reumathoid Arthritis Osteoarthrosis Chronic Back Pain Postoperative Pain
    15. 15. MOST FREQUENT SCENARIOS Inflammation Pain Accute Gout
    16. 16. Pain Treatm Goals ent Reduce discapacity Improve quality of life Use safe m edications that reduce toxic effects Less Time
    17. 17. Our m frequent problem ost s Chronic Musculoskeletal Pain
    18. 18. Our m frequent problem ost s Postraumatic Pain Postoperative Pain
    19. 19. Postoperative Pain • Pain generates em otional, physiological and psicological responses that affect the final recovery • Intensity of pain depends on the operated area: Thorax –Thoracoabdom inal Abdom –Hip & Knee –OBGYN en Low Abdom er en Osteoarticular Skin
    20. 20. Postoperative Pain Adverse Effects Respiratory Cardiovascular Gastrointestinal Urinary Neuroendocrine M etabolic Psicological
    21. 21. Pain Evaluation • Measurem of self evaluation ent • VAS –Visual Analogue Scale • Numeric verbal score • Graphic scales score • Observational Measurements • Pain Observational Scale • Toddlers Pain Scale
    22. 22. Pain As s e s s me nt
    23. 23. Pain Treatment • Opioids –System ic –Subaracnoid –Epidural • Non Opioid Analgesics –NSAIDS –Local Anesthetics • Psicological Methods
    24. 24. IAS P Po s to p Pain Pro to c o ls International Association for the Study of Pain
    25. 25. S c ale Tre atme nt International Association for the study of Pain ty Ablatio n s urg e ry si n IV Mo rphine te In Te ns in Pa Ne rve /S pinal Blo c k Opio id de rivate s NS AIDS + Co de in NS AIDS As pirin Ac e tamino phe n
    26. 26. Opioids • Obtained from Opium –Poppy flow er (natural) • Also Synthetic or sem i-synthetic • Sem i-synthetic are based on m orphin or tebain
    27. 27. Opioids Natural Synthetic Morphine Levorfanol Codein Papaverin M etadone Tebain Pentazocine Phenilpiperidines Phentanil Sufentanil Meperidine Semisynthetic Heroín Dehidrom orfin Buprenorfin
    28. 28. Opioid Effects • CNS: Pow erful analesic action – Efective pain control – Eliminates em otional side • Respiratory: depression – Dose dependent – Decreases ventilatory response to CO2
    29. 29. Opioid Effects • Muscle: – Increase of muscle tone, dose dependent • Cardiovascular – lowm iocardial depresion – reduces peripheral vascular resistance – increases venous capacity – causes bradichardia
    30. 30. Opioid Effects • Sphincter contracture – Abdom inal pain – Urinary retention • Nausea & vomit • Increase of GI secretions • Myosis
    31. 31. Don’Forget… t • Patients m have perm ust anent m edical suport • Clearly specify dose and schedule • Keep record of adverse effects and com plications • Monitor frequency and depth of respiratory m ovem ents
    32. 32. No n Opio id Analg e s ic s NS AID S S alic ilat es Paraamino fe no ls
    33. 33. Salicilates • Sir John Robert Vane • 1982 Nobel Prize • Effects of Aspirin in Pain
    34. 34. Salicilates • Ciclooxigenase non reversible inhibition , interfering with prostaglandin synthesis • Aspirin is the prototype molecule • Effects: control of pain, fever and inflam ation m • M significative side effect: erosive gastritis and GI bleeding ost • Inhibits platelet function for 7 days • Com on hypersensitivity and alergic reactions m
    35. 35. Para-Amino- Phenols • Good pain and fever control • No anti-inflam atory effects m • No peripheral ciclooxigenase inhibition • M w ost idely used analgesic in the world • High doses or long lasting treatments m cause liver toxicity ay
    36. 36. NSAIDS Non Steroidal Pharm acologic Agents that act on Pain and Inflam ation Pathw m ays
    37. 37. Inflam ation m Represents the first step in tissue repair, when the chem ical mediators produce increased blood flow capillary , perm eability, coagulation, edem and a, cell m igration The s e e ffe c ts s timulate pain no c ic e pto rs pe rmane ntly
    38. 38. Pain and Inflam ation Pathw m ays Tissue Damage Pro-Inflammatory Response Araquidonic Acid COX Prostaglandins Pain Inflammation Fever
    39. 39. NSAID Actions M NSAIDs act as non-selective inhibitors ost of the ciclooxygenase, inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzym es Cyclooxygenase catalyzes the formation of prostaglandins and throm boxane from arachidonic acid Prostaglandins act (am ong other things) as messenger m olecules in the process of inflam ation. m
    40. 40. NSAID Facts - M NSAIDs are w ost eak acids, w a pKa of 3-5 ith -They are absorbed w from the ell stomach and intestinal m ucosa. - They are highly protein-bound in plasm (>95%) a
    41. 41. NSAID Facts - M NSAIDs are m ost etabolized in the liver by oxidation and conjugation to inactive m etabolites w hich are typically excreted in the urine, although som e drugs are partially excreted in bile. -M etabolism m be ay abnorm in certain disease al states, and accum ulation m occur even w norm ay ith al dosage.
    42. 42. NS AID Fac ts - Ibuprofen and Diclofenac have short half-lives (2– hours) 3 - Coxibs have an average half-life of 24 hours - Oxicam have very long half-lives s (20– hours) 60
    43. 43. NSAIDS by chemical family Propionic acids Heteroaril- Acetic Acids – Tolmentin – Ibuprofen – Ketorolac – Phenoprofen – Ketoprofen Phenilacetics – Phlurbiprofen – Diclofenac – Naproxen Indolacetic Acids – Oxaprozin – Indom ethacin – Sulindac Pirazolones – Etodolac – Phenilbutazone
    44. 44. NSAIDS Adverse Effects The widespread use of NSAIDs has m eant that the adverse effects of these relatively safe drugs have becom increasingly prevalent. e Gastrointestinal Renal Cardiovascular Other…
    45. 45. NSAIDS Adverse GI Effects -These effects are dose-dependent -In m any cases severe enough to pose the risk of - ulcer perforation / upper GI bleeding / death - An estimated 10-20% of NSAID patients experience dyspepsia
    46. 46. NSAIDS Adverse GI Effects -2008 FDA DATA - Estimated to result in 103,000 hospitalizations and 16,500 deaths per year in the US - Represents 43% of drug-related emergency visits -M any of these events are avoidable: - Unnecessary prescriptions for NSAIDs w were ritten in 42% of visits.
    47. 47. NS AIDS Cardio vas c ular Adve rs e Effe c ts Ke arne y e t al., BMJ 2006;332:1302–1308 A re c e nt me ta -analys is o f all trials c o mparing NS AIDs fo und an 80% inc re as e in the ris k o f myo c ardial infarc tio n with bo th ne we r COX-2 antag o nis ts and hig h do s e traditio nal anti- inflammato rie s c o mpare d with plac e bo All NS AIDs are as s o c iate d with a do uble d ris k o f s ympto matic he art failure in patie nts witho ut a his to ry o f c ardiac dis e as e
    48. 48. NSAIDS Cardiovascular Adverse Effects In patients w such a history, use of NSAIDs w associated w ith as ith m than 10-fold increase in heart failure ore If this link is found to be causal NSAIDs are estim ated to be responsible for up to 20% of hospital adm issions for congestive heart failure
    49. 49. NSAIDS Renal Adverse Effects  Changes in renal haem odynam (blood ics flow ordinarily m ), ediated by Prostaglandins Prostaglandins norm ally cause vasodilation of the afferent arterioles of the glomeruli This helps m aintain norm glom al erular perfusion and glom erular filtration rate (GFR), an indicator of renal function
    50. 50. NSAIDS Renal Adverse Effects In renal failure the kidney is trying to m aintain renal perfusion pressure by elevated Angiotensin II levels Angiotensin II also constricts the afferent ateriole into the glom erulus in addition to the efferent arteriole it norm ally constricts
    51. 51. NSAIDS are good, but m research is needed ore to im prove safety and increase efficacy
    52. 52. Discovery of COX-2 Selective inhibition of COX-2 results in anti-inflam atory m action w ithout disrupting gastroprotective prostaglandins. Daniel L. Sim ons m Brigham Young University
    53. 53. Discovery of COX-2 COX-1 is a constitutively expressed enzym e w a quot;house-keepingquot; role ith in regulating many norm physiological al processes COX-2 is an enzym expressed in e inflam ation m and it is inhibition of COX-2 that produces the desirable effects of NSAIDs.
    54. 54. Discovery of COX-2 OXICAM and COXIBS S Proved Efficacy and Safety FDA and EM approval under revision EA due to validation of Cardiovascular Adverse Effects
    55. 55. MYOCHRYSINE 1936 CORTONE M 1949 HYDROCORTONE 1952 DECADRON 1958 INDOCID 1965 (Indometacina) 1978 CLINORIL (Sulindac) DOLOBID 1982 (Diflunisal) VIOXX (Rofecoxib) 1998 SD: pain research tradition ARCOXIA 2002 (Eto ric o xib )
    56. 56. ARCOXIA Etoricoxib S O 2 CH3 Cl N N CH3
    57. 57. Etoricoxib world clinical program Accute Pain Chronic Pain – Post dental surgery pain – Osteoarthritis – Postoperative pain – Chronic LowBack Pain – Gout arthritis accute pain – Rheum athoid Arthritis
    58. 58. Etoricoxib world clinical program Phas e I / Pharmac o lo g y: 651 subjects Phas e II / Clinic al: OA, RA : 4888 patients. EDGE: GI tolerance: 2 studies >30.000 OA: 3953 patients, 90 mg RA: 2032 patients, 90 mg. MEDAL: CV safety OA: 8940 patients (6769:60m 2171: 90m g; g) RA: 2846 patients, 90 mg.
    59. 59. Po s tOp Pain Re s ults Max Pain Relief Score 3.5 Cambio promedio con ± EE 3.0 ETORICOXIB 120 mg 2.5 2.0 ETORICOXIB 60 mg 1.5 Ibuprofen 400 mg 1.0 Placebo 0.5 0.0 0 1 2 3 4 5 6 7 8 12 24 Time (hr) Initial Analgesic Effect with Etoricoxib 120 mg= 24 min Initial Analgesic Effect with Ibuprofen 400 mg.= 32 min Clin Therapeutics 2004;26:667-672.
    60. 60. PostOp Pain Results Average Pain Relief Score 3.5 Puntuación promedio de AD ± 3.0 2.5 ETORICOXIB 120 mg Naproxen 2.0 550 mg 1.5 Paracetamol 600mg /codeín 1.0 60 mg EE 0.5 Placebo 0.0 0 1 2 3 4 5 6 7 8 10 12 20 24 Time (Hours) Post-dose
    61. 61. Po s tOp Pain Re s ults Ortho pe dic S urg e ry • TKR & THR • Post Arthroscopy pain • Accute Phase: • Sym to Naproxen 1 gm ilar . • 2 - 7° day: • Better analgesic effect •Low need for other analgesics er 120 mg/day Anesth Analg 2005;101:1104-11. Act Anaesthesiol Scand 2007;51:316-321.
    62. 62. PostOp Pain Results 3.5 3.0 2.5 Puntuación ±EE ETORICOXIB120 2.0 mg (n=100) 1.5 Oxicodone/paracetamol 10/650< mg (n=100) 1.0 Placebo (n=25) 0.5 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 Time (Hours) Post-dose
    63. 63. PostOp Pain Results W “ as Rescue” edication needed ? m 100 % Patients that required rescue medication 90 72.0 80 70 Porcentaje ±SE 60 50 41.0** 40 30 22.0* 20 10 0 Etoricoxib 120 mg Oxicodone/Paracetamol Placebo (n=100) 10/650 mg (n=25) (n=100) *p<0.010 para Etoricoxib vs. oxicodona/paracetamol; p<0.001para Etoricoxib vs. placebo **p<0.010 para oxicodona/paracetamol vs. placebo
    64. 64. Tolerance Profile Vs. Oxicodone Adverse effects results Oxicodone/ Eto ric o xib paracetam ol 120 mg 10/650 mg Placebo (%) patients (n=100) (n=100) (n=25) Any AE 32 (32.0)** 71 (71.0) 6 (24.0) AE related to treatment 9 (9.0)** 64 (64.0) 2 (8.0) Com on AE m Dizziness 2 (2.0) 38 (38.0) 1 (4.0) Nausea 4 (4.0)** 33 (33.0) 0 (0.0) Vom it 0 (0.0)** 20 (20.0) 0 (0.0) Drow siness 0 (0.0) 19 (19.0) 1 (4.0) Post Op Alveolitis 15 (15.0) 15 (15.0) 2 (8.0) Headache 3 (3.0) 6 (6.0) 0 (0.0)
    65. 65. Etoricoxib Farmacokinetics Concentration M 1h ax. Biodisponibility 100% D o s tic s ne Not affected by Ki Stable after 7 days Dose r e nea food intake Li Effects Lasts 24 hs (72%) Concentration Effect Starts at 24 M inutes (50%)
    66. 66. Eto ric o xib Me tabo lis m Lowinteraction potential Elimination: M etabolized by several P450 system - 70% renal enzym es: - 20% feces CYP3A4 (∼60%) y CYP2D6, - <2% unaltered CYP2C9, CYP1A2 y CYP2C19
    67. 67. Medication Interaction MEDICATION EFFECT Ketoconazol, ASA, No effect Anti-H2, prednisona. ↓ 65% plasma concentration of ↑ Do s e Rifampicin Etoricoxib. Warfarin 120 mg of Etoricoxib ↑ 13% INR. INR Diuretics, IECAs y Al NSAIDS may ↓ anti-HBP effects ARA II Mo nito r BP No interaction with 60 y 90 mg. 120 mg Mo nito r Metotrexate increases MTX levels 28% MTX Birth control pills Increase de ethinil estradiol (50- 60%). -HRT Mic ro do s is
    68. 68. S afe ty Pro file Adverse effects 7.0 5.9 6.0 5.4 5.0 4.6 4.0 3.6 3.5 % 3.0 2.0 1.0 0.0 Cefalea Infeccón TRS Diarrea HTA Náusea
    69. 69. S afe ty Pro file Adverse Effects 8.5 9 7.5 8 6.5 7 5.8 6 4.8 4.8 5 4.1 4.3 3.4 4 3 2.1 2.1 % 2 1.2 1.1 0.9 1.2 0.1 0.4 0.4 1 0 ARXOXIA 90 ARCOXIA 60 ARCOXIA 120 NAPROXENO IBUPROFENO Placebo 2400 mg 1g Retired due to AE EA TGI. EA HTA
    70. 70. GI Adve rs e Effe c ts Patients with gastric ulcers or erosions diagnosed with endoscopy 100 100 90 90 80 80 72.0 70 70 60 60 58.7 50 50 Incidencia (%) Incidencia (%) 40 40 30 23.2* 22.7* 30 19.7* 17.4* 20 20 10 10 0 0 Placebo Etoricoxib Naproxeno Placebo Etoricoxib Ibuprofeno (n=229) 120 mg 1000 mg (n=221) 120 mg 2400 mg (n=236) (n=235) (n=216) (n=218) AR - OA 12 weeks treatment OA *p<0.001 para placebo y etoricoxib vs. naproxeno
    71. 71. Endo s c o py s tudie s c o mparing Eto ric o xib in OA & RA Incidence of GI Ulcers ≥3 mm - 12 weeks 35 25 30 25.27 20 17.02 Incidencia Acumulada, Incidencia Acumulada, 25 porcentaje (± IC 95%) porcentaje (± IC 95%) 20 1 5 15 1 8.12*** 10 0 7.42* 5 5 1.35* 1.86** 0 0 Placebo Etoricoxib Naproxeno Placebo Etoricoxib Ibuprofeno (n=247) 120 mg 1000 mg (n=233) 120 mg 2400 mg (n=251) (n=244) (n=221) (n=226) OA o AR OA *p<0.001 vs. naproxeno; **p<0.001 vs. ibuprofeno; ***p=0.007 vs. ibuprofeno Datos en Archivo, MSD.
    72. 72. Cardio vas c ular adve rs e e ffe c ts Pbo 60 mg 90 mg Naproxen N=1011 N=658 N=889 N=790 Incidence (%) HBP related AE 2.0 4.7 4.5* 3.5 HBP 1.5 4.0 3.3 2.8 Treatment 0.0 0.3 0.3 0.4 suspended due to HBP (%) Pbo 60 mg 90 mg Naproxeno N=1011 N=658 N=889 N=790 Incidence (%) Edema related AE 2.1 4.0 2.9 2.9 Lower Limb 1.9 3.2 1.3 2.3 Edema Treatment 0.3 0.3 0.2 0.1 suspended due to Lower Limb Edema (%) Note: * p<0.05 vs. Pbo
    73. 73. Us e with c autio n … Hiperlipidem heavy sm ia, okers Pregnancy: 6-9 month Severe renal Insufficiency Alergies Dehidration Moderate liver insufficicency
    74. 74. Co ntraindic atio ns – Specific Hypersensitivity or Allergy – Gastric Ulcer, GI Bleeding or acido-peptic disease history – Congestive Heart Insufficiency or ventricular disfunction – Uncontrolled HBP – Coronary syndrom –coronary surgeries es – Severe liver disfunction – Pregnancy – Children
    75. 75. Etoricoxib In ac c ute pain 120 m once a day g
    76. 76. Etoricoxib In Rhe umatho id Arthritis 90 m once a day g
    77. 77. Etoricoxib in Os te o arthro s is 60 m once a day g
    78. 78. Etoricoxib In c hro nic lo w bac k pain 60 m once a day g
    79. 79. Co nc lus io n I us e Eto ric o xib be c aus e … – Pow erful, quick and long lasting analgesic – Strong Anti - inflam atory m – Safe m edication – W supported by basic and clinical research ell – Backed up by a w know researcher in the industry ell n – Better than any other product I can prescribe An e xc e lle nt s o lutio n fo r many o f my pro ble ms …
    80. 80. I’ used Etoricoxib ve on myself… .
    81. 81. “ the neww In orld there w be no pain… ” ill Apc 7,17;21,4
    82. 82. Thanks !
    83. 83. Thanks !
    84. 84. Thanks !
    85. 85. nfo ? .org ore Imedical M ay nw om l. c leal@fe al@gmai le chaz

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