Prophylactic oral ibuprofen or ibuprofen-codeine versus placebo for postoperative pain after primary hip arthroplasty.

Transkript

1 Prophylactic oral ibuprofen or ibuprofen-codeine versus placebo for postoperative pain after primary hip arthroplasty. Dahl V, Raeder J, Drøsdal S, Wathne O, Brynildsrud J. Acta Anaesthesiol Scand Apr;39(3): hofteprotese op. pasienter spinal bupivakain anestesi -Postop. enkeltdose per os: ibuprofen 800 mg vs. ibuprofen m/60 mg kodein vs placebo -Observasjon i 5 timer Resultater: -Placebo pas hadde mer smerte -Placebo pas fikk 45% mer opioid (ketobemidon) rescue -Ingen forskjell i kvalme, blødning, andre bivirkninger -Kodein ga ingen tillegsgevinst (eller ulempe)

2 Post-operative bleeding, hip arthroplasty: Slappendel R et al. Eur J Anaesthesiol 2002:19: patients, total hip replacement, spinal anaesthesia, same surgeon: Pretreatment for 2 weeks with either placebo or ibuprofen 600 mg x 3 Ibuprofen (n=17) Placebo (n=19) Blood loss - during surgery 700 ± ± 203 P< after surgery 461 ± ± 169 ns - total 1161 ± ± 337 P<0.05 Number transfusions 9 6

3 Post-operative bleeding, hip arthroplasty: Slappendel R et al. Eur J Anaesthesiol 2002:19: patients, total hip replacement, spinal anaesthesia, same surgeon: Pretreatment for 2 weeks with either placebo or ibuprofen 600 mg x 3 Ibuprofen (n=17) Placebo (n=19) Blood loss - during surgery 700 ± ± 203 P< after surgery 461 ± ± 169 ns - total 1161 ± ± 337 P<0.05 Number transfusions 9 6

4 COX-2 HEMMERE VS NSAIDS: ingen effekt på blodplater (dvs. blødning) sign.reduksjon i gastrointestinale sår mindre allergi sterkere reseptorbinding (lengre durasjon) MEN: Risiko for nyre svikt Risiko for hypertensjon / hjerte svikt

5 Prophylactic oral ibuprofen or ibuprofen-codeine versus placebo for postoperative pain after primary hip arthroplasty. Dahl V, Raeder J, Drøsdal S, Wathne O, Brynildsrud J. Acta Anaesthesiol Scand Apr;39(3): hofteprotese op. pasienter spinal bupivakain anestesi -Postop. enkeltdose per os: ibuprofen 800 mg vs. ibuprofen m/60 mg kodein vs placebo -Observasjon i 5 timer Resultater: -Placebo pas hadde mer smerte -Placebo pas fikk 45% mer opioid (ketobemidon) rescue -Ingen forskjell i kvalme, blødning, andre bivirkninger -Kodein ga ingen tillegsgevinst (eller ulempe)

6 TELEFON, 24 T POST.OP, % smerte(medium/mye), PARAC+CODEIN TABL(nx10): ALL Hernia Anal Fj. osteosyn. Ost.r Osteo-tomi Ost.t Kne a.skopi Knee Dupuy Gangl P+C TABL PAIN Ullevaal, data on file Varic Cholec

7 KODEIN (60mg) + PARACET.(800mg) ELLER IBUPROFEN (800mg) x 3 HJEMME: Ræder J, Steine S, Vatsgar T. Anesth Analg 2001:92: pas, hernie/varice kir.; gen.anestesi dobbel-blindt 3 dager hjemme pat denied participation due to distrust in codeine+paracet. Identical analgesia in both groups 20-30% more nausea with codeine+paracet. More obstipation with codeine+paracet (23% no defec. for 3d) More general satisfaction with Ibuprofen

8 Increased risk of chronic pain genetic disposal pain at other site before surgery female gender depressive state general anaesthesia* (vs. spinal) nerve damage re-operation strong postoperative pain radiation damage Kehlet H et al. Lancet 2006:367: and *Brandsborg B et al Anesthesiology

9 KODEIN (60mg) + PARACET.(800mg) ELLER IBUPROFEN (800mg) x 3 HJEMME: Ræder J, Steine S, Vatsgar T. Anesth Analg 2001:92: pas, hernie/varice kir.; gen.anestesi dobbel-blindt 3 dager hjemme pas nektet å delta, (tidl. kvalme eller dårlig effekt av kodein+paracet.) Identisk analgesi i begge grupper (hvile/provokasjon, dag/natt, peak/mean) 20-30% flere med kvalme i kodein+paracet. gruppen Mere obstipasjon med kodein+paracet (23% uten defec. for 3d) Mere general tifredshet med smertelindring med Ibuprofen

10 Acta Anaesthesiol Scand Apr;39(3): Prophylactic oral ibuprofen or ibuprofen-codeine versus placebo for postoperative pain after primary hip arthroplasty. Dahl V, Raeder JC, Drøsdal S, Wathne O, Brynildsrud J. The postoperative analgesic effect of ibuprofen was compared with a combination of ibuprofen and codeine versus placebo. The study was prospective, randomized, double blind with 123 consecutive hip arthroplasty operations. All the patients received oral diazepam as premedication and spinal anaesthesia with bupivacaine 5 mg/ml 3-4 ml. Postoperatively, when the spinal anaesthesia started to wear off, the patients were randomly assigned to one of three groups; the ibuprofen group (n = 48) received 800 mg of ibuprofen orally. The ibuprofen/codeine group (IC, n = 48) received 800 mg of ibuprofen combined with 60 mg of codeine. The placebo group (P, n = 25), received oral placebo medication. The patients were observed for the need of additional opioid (e.g. ketobemidone), pain score (verbal and VAS), bleeding and side effects for five hours. The patients in the placebo group (P) had significantly higher pain scores (P < 0.05) compared with the two other groups after 2 and 4 hours, with no significant differences after 1, 3 and 5 hours. The P group also received 45% more opioids (P < 0.001) compared with the two other groups during the same period. No significant differences in bleeding or side-effects were observed between the groups. There were no significant differences between the ibuprofen group and the ibuprofen/codeine group. We conclude that a prophylactic dose of 800 mg ibuprofen orally has an opioid sparing effect with a tendency of less pain experience during the first hours after hip arthroplasty.

11

12

13 NSAIDs og glukokortikoider til smertebehandling av ortopedkirurgiske pasienter PRO! Johan Ræder Anestesiavd. / UiO Oslo Universitets Sykehus, Avd. Ullevål, Oslo mail: johan.rader@medisin.uio.no

14 NSAIDs og ortopedisk kirurgi? Hvorfor kan vi ikke bare droppe NSAIDs til disse pasientene? 1. Ortopediske pasienter har mye postoperativ smerte 1. Inadekvat smertelindring har uheldige konsekvenser - Subjektivt ubehag - Redusert opptrening, forsinket recovery - Mer kroniske smerter 3. Forbud mot NSAID fører til økt bruk av opioider - Opioide bivirkninger

15 Opioid problemer Toleranseutvikling Hyperalgesi utvikling Bivirkninger Kvalme, obstipasjon, avhengighet, sedasjon, kløe, søvnvansker Respirasjonsdepresjon Individuelle variasjoner i reseptor (genetisk) Variabel enteral absorbsjon Mindre effektive ved bevegelsesindusert smerte Immundepresjon (infeksjon? cancer?) men... Tar all smerte hvis bare dosen er høy nok Bivirkningsterskel følger toleranse (unntak: obstipasjon) Relativt rimelige

16

17

18 22 studier, pasienter: Signifikant reduksjon med NSAID vs placebo: -Kvalme: 12% -Oppkast: 32% -Sedasjon: 29%

19 Opioid problemer Case 1: - Hofteprotese pasient som ligger utover ettermiddagen, dag 2 på PO: smerter, opiod, kvalm, trett Ikke postklar - Ketorolac iv: mindre smerte, redusert opioid, postklar Case 2: - Ung (12 år) rotasjonsosteaotomi, som ligger utover ettermiddagen, dag 2 på PO: smerter, opiod, kvalm, trett Ikke postklar - Ketorolac iv: mindre smerte, redusert opioid, postklar Case 3: - Pasient med kneprotese på post; mye vondt, paracetamol + opioid respirasjonsstans på post - Videre behandling m/paracet+ NSAID

20 Pain as a factor complicating recovery and discharge after ambulatory surgery: Pavlin J et al. Anesth Analg 2002:95: patients, mixed surgery, general anaesthesia, 0-3 h observation post-op.: 24% of patients delayed recovery unit stay due to pain 42% less opioid need when NSAID (ketorolac) was used

21 NSAIDs og Ben sene tilheling

22 Faktorer som påvirker bentilheling: Tobakks røyking Ernæring Alder Diabetes mellitus Reumatoid artrit Osteoporose Opptrening Bevegelse/belastning Cytostatika Systemiske glukokortikoider NSAID

23 NSAID og Ortopedi: - Hva er problemet? PHOSFOLIPID phosfolipase LEUKOTRIEN ARACHIDONIC ACID PROSTAGLANDIN Cox-II Cyclo-oxygenase Cox-I PROSTAGLANDIN substrate activator VEVS HOMEOSTASE nyrer GI-mucosa trombocyter

24 NSAID og Ortopedi: - Hva er problemet? CELLE traume PHOSFOLIPID phosfolipase smerte inflammasjon LEUKOTRIEN ARACHIDONIC ACID PROSTAGLANDIN Cox-II Cyclo-oxygenase Cox-I PROSTAGLANDIN substrate activator PARACETAMOL? smerte inflammasjon allergi? VEVS HOMEOSTASE nyrer GI-mucosa trombocyter

25 NSAID og Ortopedi: - Hva er problemet? CELLE traume PHOSFOLIPID phosfolipase EFFEKTER CORTICO STEROID smerte inflammasjon LEUKOTRIEN smerte inflammasjon allergi? ARACHIDONIC ACID Cox-II Cyclo-oxygenase Cox-I? PROSTAGLANDIN VEVS HOMEOSTASE nyrer GI-mucosa trombocyter PROSTAGLANDIN NSAID COXIB substrate activator PARACETAMOL?

26 NSAID og Ortopedi: - Hva er problemet? LEUKOTRIEN smerte inflammasjon allergi? CELLE traume PHOSFOLIPID phosfolipase ARACHIDONIC ACID Cox-II Cyclo-oxygenase Cox-I? PROSTAGLANDIN VEVS HOMEOSTASE nyrer GI-mucosa trombocyter BIVIRKNINGER CORTICO STEROID PROSTAGLANDIN NSAID COXIB smerte Inflammasjon Vevstilheling substrate activator PARACETAMOL?

27 LEUKOTRIENER VEV (skade) FOSFOLIPID fosfolipase ARAKIDONSYRE PROSTAGLANDIN BIVIRKNINGER??? Cox-II Cyclo-oksygenase Cox-I STEROID Cox-2 hemmer PROSTAGLANDIN smerte inflammasjon tilheling? substrat aktivator PARACETAMOL smerte Inflammasjon allergi VEVSHOMEOSTASE nyrer GI-slimhinne trombocyter NSAID

28 Prostaglandiner og bentilheling: - Øker osteoblast aktivitet - Reduserer osteoklast aktivitet COX-1-knock-out mice have normal callus formation and fracture healing COX-2- knock-out mice have delayed callus formation and fracture healing Simon et al.: COX-2 function is essential for bone fracture healing. JBMR 17 (2002)

29 Cox I hemming Indometacin Ketorolac Naproxen (Indocid) (Toradol) (Naprosyn) Ibuprofen (Ibux, Brufen etc) Diclofenac Celecoxib (Voltaren, Diklofenak) (Celebra) Trombocyteffekt + Trombocyteffekt Cox II hemming Parecoxib Rofecoxib Etoricoxib Lumiracoxib (Dynastat) (Vioxx)) (Arcoxia) ((Prexige))

30 Dyrestudier..

31 Inhibition of fracture healing by indomethacin in rats. Sudmann E, Dregelid E, Bessesen A, Mørland J Eur J Clin Invest. 1979:9: Indomethacin 2 mg/kg/d, 205 rotter, ikke-fikserte femurfrakturer, placebo kontroll -En serie med 29 d behandling en (to!) serie med 7 dager behandling fulgt i dager Resultat / Konklusjon: Forsinket tilheling, økt feilstilling og mer ustabil fraktur med behandling (begge serier) 7 dagers behandling tilheling (stabil + kallus bro med kalk) etter dager: - 53% etter indomethacin - 68% etter placebo (P=0.03)

32 Inhibition of fracture healing by indomethacin in rats. Sudmann E, Dregelid E, Bessesen A, Mørland J Eur J Clin Invest. 1979:9: Indomethacin 2 mg/kg/d, 205 rotter, ikke-fikserte femurfrakturer, placebo kontroll -En serie med 29 d behandling en (to!) serie med 7 dager behandling fulgt i dager Resultat / Konklusjon: Forsinket tilheling, økt feilstilling og mer ustabil fraktur med behandling (begge serier) 7 dagers behandling tilheling (stabil + kallus bro med kalk) etter dager: - 53% etter indomethacin - 68% etter placebo (P=0.03)

33 Negative effect of parecoxib on bone mineral during fracture healing in rats Dimmen S, Nordsletten L, Engebretsen L, Steen H and Madsen JE Acta Orthopaedica 2008,79:3, x 26 rotter med parecoxib 0,5 mg/kg intraperit. x 2, i 7 dager, start pre-op (fraktur) - Bentetthet, 2, 3 og 6 uker; - Styrketesting v/ 6 uker Resultat / Konklusion: Parecoxib given postoperatively for a week has a negative effect on mineralization during the early phase (week 2 and 3) of fracture healing.

34 Negative effect of parecoxib on bone mineral during fracture healing in rats Dimmen S, Nordsletten L, Engebretsen L, Steen H and Madsen JE Acta Orthopaedica 2008,79:3, x 26 rotter med parecoxib 0,5 mg/kg intraperit. x 2, i 7 dager, start pre-op (fraktur) - Bentetthet, 2, 3 og 6 uker; - Styrketesting v/ 6 uker Resultat / Konklusion: Parecoxib given postoperatively for a week has a negative effect on mineralization during the early phase (week 2 and 3) of fracture healing.

35 Negative effect of parecoxib on bone mineral during fracture healing in rats Dimmen S, Nordsletten L, Engebretsen L, Steen H and Madsen JE Acta Orthopaedica 2008,79:3, x 26 rotter med parecoxib 0,5 mg/kg intraperit. x 2, i 7 dager, start pre-op (fraktur) - bentetthet, 2, 3 og 6 uker; styrketesting v/ 6 uker Høy verdi er best

36 Negative effect of parecoxib on bone mineral during fracture healing in rats Dimmen S, Nordsletten L, Engebretsen L, Steen H and Madsen JE Acta Orthopaedica 2008,79:3, x 26 rotter med parecoxib 0,5 mg/kg intraperit. x 2, i 7 dager, start pre-op (fraktur) - bentetthet, 2, 3 og 6 uker; styrketesting v/ 6 uker Interpretation: - No mechanical differences were detected between the control and treatment groups after 6 weeks, but they may have been present earlier in the fracture healing process.(!) Høy verdi er best - Our findings do, however, indicate that parecoxib given postoperatively for a week has a negative effect on mineralization during the early phase of fracture healing.

37 Negative effect of parecoxib on bone mineral during fracture healing in rats Dimmen S, Nordsletten L, Engebretsen L, Steen H and Madsen JE Acta Orthopaedica 2008,79:3, x 26 rotter med parecoxib 0,5 mg/kg intraperit. x 2, i 7 dager, start pre-op (fraktur) - bentetthet, 2, 3 og 6 uker; styrketesting v/ 6 uker. The mechanical strength was reduced after 6 weeks, but the study lacked sufficient statistical power to show the statistical significance of this finding.. Høy verdi er best We were able to confirm that parecoxib given for only a few days affects bone metabolism.* * Reelt eller surrogat outcome?

38 Fluor in the treatment of osteoporosis. An overview of thirty years clinical research. Dequeker J, Declerck K Schweiz Med Wochenschr Nov 27;123(47): Links -Fluoride has a positive effect on axial bone density,. but the axial bone gain is not matched by similar changes in cortical bone -In two controlled fluoride therapy studies the incidence of vertebral fractures decreased, while in two other studies it increased. - Experience teaches that denser bones are not necessarily better bones.

39

40

41 Problemer med Dyr Menneske: Hva er ekvipotente doser? Hva er sammenlignbar post-frakturfase og behandlingslengde? ( alt går 2-3 ganger fortere hos rotte?) Hva er sammenlignbar post-fraktur oppførsel? Ro, hvile, fraktur immobilisering Opptrening, fysioterapi Andre faktorer: Biologisk alder, ernæring, bentetthet.. Statistisk styrke etikk: Reell non-union sjelden (rtg.logisk hyppig relevans?)

42 Humane prospektive dobbeltblinde kliniske studier:

43 Scoliose kirurgi: - sensitiv modell for tilheling av frakturer i spongiøst vev

44 Peri-operative NSAIDs or coxibs in patients for posterior spinal fusion: 1 yr Non-union rate: 1 Glassman et al, Spine 1998; 23: 834: 60mg loading + 30 mg x 4, for 3 days +/- Reuben et al, Reg Anesth Pain Med 2001; 26 (Suppl. 1): 49

45 Ketorolac and spinal fusion: Does the perioperative use of ketorolac really inhibit spinal fusion? Pradhan BB, Tatsumi RL, Gallina J, Kuhns CA, Wang JC, Dawson EG Spine 2008:33:

46 Ketorolac and spinal fusion: Does the perioperative use of ketorolac really inhibit spinal fusion? Pradhan BB, Tatsumi RL, Gallina J, Kuhns CA, Wang JC, Dawson EG Spine 2008:33:

47 Ketorolac and spinal fusion: Does the perioperative use of ketorolac really inhibit spinal fusion? Pradhan BB, Tatsumi RL, Gallina J, Kuhns CA, Wang JC, Dawson EG Spine 2008:33:

48 Piroxicam (20 mg) and Colles fracture Study: Results: Randomised, double-blind trial Piroxicam 20 mg/placebo daily for 8 weeks (n=42 women) in postmenopausal women Less pain in the NSAID-group compared to the placebo group No differences or decrease in fracture healing No difference in bone mineral density P Adolphson et al. No effects of piroxicam on osteopenia and recovery after Colles' fracture. Arch Orthop Trauma Surg :

49 NSAIDs/COXIBs and Total Hip Replacement Follow up: 65 mths (60-71 mths) Prophylaxis with Indomethacin 100 mg (n = 134) Control group without any prophylaxis (n=44) Early Loosening 0 1 Revision 0 0 Trnka et al.: Stable bony integration with and without short-term indomethacin prophylaxis. Arch Orthop Trauma Surg 119 (1999)

50 NSAIDs/COXIBs and Total Hip Replacement (Follow up: 6 mths Zacher J data on file) Prophylaxis with Diclofenac 2x75 mg (n = 168) Rofecoxib 1 x 25 mg (n=101) Early Loosening 0 0 Revision 0 0 In our database of prospective studies with NSAIDs/COXIBs and THR there are no signs of compromising bony ingrowth of the implants

51 -Kneprotese kirurgi, 2 x 35 pas -50 mg rofecoxib 1d + 1 t preop + 5 dager, deretter 25 mg daglig i 8 dager vs placebo Fordeler (sign) m/rofecoxib: - Mindre smerte første uke - Mindre kvalme og søvnforstyrrelse - Bedre knefleksjon, mindre behov for fysioterapi etter 1 mnd

52 -Kneprotese kirurgi, 2 x 35 pas -50 mg rofecoxib 1d + 1 t preop + 5 dager, deretter 25 mg daglig i 8 dager vs placebo Fordeler (sign) m/rofecoxib: - Mindre smerte første uke - Mindre kvalme og søvnforstyrrelse - Bedre knefleksjon, mindre behov for fysioterapi etter 1 mnd

53

54 The effect of initiating a preventive multimodal analgesic regimen on long-term patient outcomes for outpatient anterior cruciate ligament reconstruction surgery. Reuben SS, Ekman Anesth Analg. 2007;105: korsbåndsopererte - alle fikk lokal an i ledd + kjøling v/kir avslutning - Alle fikk paracetamol 1g preop og deretter 1g x 4 i 14 dager -Randomisert til Celecoxib 400 mg preop + deretter 200 mg x 2 i 14 dager eller -Placebo Resultat / Konklusjon v/ kontroll etter 6 mnd: Flere patellofemorale komplikasjoner m/ placebo (P=0.001): - anterior knee pain 15% vs 1% - complex regional pain syndrome 7% vs 1% - flexion contractures 9% vs 2% - scar tissue requiring re-arthroscopy 8% vs 2% Færre med forbedret aktivitetsnivå: 65% vs 84% - Færre klarte intens aktivitet (P < 0.02), og full sportslig aktivitet (P < 0.05).

55 The effect of initiating a preventive multimodal analgesic regimen on long-term patient outcomes for outpatient anterior cruciate ligament reconstruction surgery. Reuben SS, Ekman Anesth Analg. 2007;105: korsbåndsopererte - alle fikk lokal an i ledd + kjøling v/kir avslutning - Alle fikk paracetamol 1g preop og deretter 1g x 4 i 14 dager -Randomisert til Celecoxib 400 mg preop + deretter 200 mg x 2 i 14 dager eller -Placebo Resultat / Konklusjon v/ kontroll etter 6 mnd: Flere patellofemorale komplikasjoner m/ placebo (P=0.001): - anterior knee pain 15% vs 1% - complex regional pain syndrome 7% vs 1% - flexion contractures 9% vs 2% - scar tissue requiring re-arthroscopy 8% vs 2% Færre med forbedret aktivitetsnivå: 65% vs 84% - Færre klarte intens aktivitet (P < 0.02), og full sportslig aktivitet (P < 0.05).

56 Anesth Analg. 2008;106:

57 A prospective Randomized Trial on the Role of Perioperative Celecoxib Administration for Total Knee Artroplasty: Improving Clinical Outcome Reuben SS, Buvenandran A, Katz B, Kroin JS. Anesth Analg 2008:106: pasienter, alle m/ pasient kontrollert epidural analgesi post.op. i 2 døgn - Celecoxib: 100 mg x 2 uken før, 400 mg rett før, 200 mg x 2 i 10 dager etterpå vs placebo Resultat - Fordeler (sign) m/ Celecoxib: -Mindre behov for epidural analgesi -Mindre behov for oxykodon hjemme -Bedre bøyefunksjon første 3 dager -Raskere full felksjon (90 ) -Mindre kvalme, oppkast, kløe postop -Bedre knefunksjon v/ ett års kontroll

58 A prospective Randomized Trial on the Role of Perioperative Celecoxib Administration for Total Knee Artroplasty: Improving Clinical Outcome Reuben SS, Buvenandran A, Katz B, Kroin JS. Anesth Analg 2008:106: pasienter, alle m/ pasient kontrollert epidural analgesi post.op. i 2 døgn - Celecoxib: 100 mg x 2 uken før, 400 mg rett før, 200 mg x 2 i 10 dager etterpå vs placebo Resultat - Fordeler (sign) m/ Celecoxib: -Mindre behov for epidural analgesi -Mindre behov for oxykodon hjemme -Bedre bøyefunksjon første 3 dager -Raskere full fleksjon (90 ) -Mindre kvalme, oppkast, kløe postop -Bedre knefunksjon v/ ett års kontroll

59

60 Hva gjør vi??

61 Prospect project - Procedure specific evidence based recommendations on postoperative pain management - 4 surgeons (Kehlet at al) + 6 anasthesiologists (Rawal et al.) - Evidence based Cochrane approach (Grade A-D evidence) Abdominal hysterctomy Herniorraphy Laparoscopic cholecystect Open colonic resection Thoracotomy Total hip arthroplasty Total knee arthroplasty

62 Total Knee Arthroplasty Postoperative: Systemic analgesia: Conventional NSAID/COX-2-selective inhibitors (Grade A) + strong opioids (Grade A), titrated to effect (for high intensity pain) + paracetamol (Grade B) Conventional NSAID/COX-2-selective inhibitors (Grade A) +/- weak opioids (Grade B), titrated to effect (for moderate or low intensity pain) + paracetamol (Grade B) Regional analgesia: - Femoral nerve block (Grade A) Continuous passive motion (for reasons other than analgesia) (Grade A) Intensive rehabilitation (for reasons other than analgesia) (Grade D) Postoperative Systemic analgesia Total Hip Arthroplasty COX-2-selective inhibitors (grade A) or conventional NSAIDs (grade B) (depending on patient risk factors) in combination with strong or weak opioids, as required for pain intensity Strong opioids (grade B) in combination with non-opioid analgesia for high-intensity pain, preferably administered intravenously by patientcontrolled analgesia (grade B) or fixed-interval injection (grade D) Weak opioids for moderate- or low-intensity pain (grade A) if conventional NSAIDs or COX-2-selective inhibitors are not sufficient or are contraindicated Paracetamol (grade A) for all pain intensities in combination with conventional NSAIDs or COX-2-selective inhibitors (with or without weak opioids)

63 Prof. Alain Borgeat, Professor/Chairman Balgrist University Orthopedic Hospital, Zurich Editor, Anesthesiology: We use NSAID or coxib to all postoperative orthopedic patients for one week, only exception is rotator-cuff surgery

64 Prosedyre for ikke-opioid postoperativ smertelindring, ortopediske pasienter: Oslo Universitets Sykehus Anestesi /Ortopedisk kir avd Ullevål Sept-08 Ortopedisk betingede kontraindikasjoner er mye basert på dyrestudier og eksperimentelle studier; ut fra føre var prinsippet, i en situasjon hvor det er lite kliniske studier foreløpig som viser skadelige effekter. Hos pasienter hvor annen god smertelinding er vanskelig å få til eller er utilstrekkelig, kan på individuelt grunnlag ortoped og anestesilege i samråd forordne disse midlene utover relative kontraindikasjoner for en kort periode. Spesifikke kontraindikasjoner:??

65

66 Takk! mail: no

67 Da er vel alt greit?

68 Prosedyre for ikke-opioid postoperativ smertelindring, ortopediske pasienter: Ullevål Universitets Sykehus Anestesi /Ortopedisk kir avd Sept-08 Ortopedisk betingede kontraindikasjoner er mye basert på dyrestudier og eksperimentelle studier; ut fra føre var prinsippet, i en situasjon hvor det er lite kliniske studier foreløpig som viser skadelige effekter. Hos pasienter hvor annen god smertelinding er vanskelig å få til eller er utilstrekkelig, kan på individuelt grunnlag ortoped og anestesilege i samråd forordne disse midlene utover relative kontraindikasjoner for en kort periode. Spesifikke kontraindikasjoner: - Skaftfrakturer i: humerus, radius, ulna, femur, tibia, fibula og metatars. Det gjelder kun frakturer i skaftet, dvs. diafysen, og ikke f.eks. distale radiusfrakturer og ankelfrakturer. - Frakturer og seneskader i hånden. - Stressfrakturer - Avstivning av ryggraden (alle typer) -Osteotomi og artrodese (alle typer) - Fractura colli femoris operert med osteosyntese. - Operasjoner for pseudartrose - Senetilheling og sene-ben tilheling. Inkluderer rotatorcuffsuturer og korsbåndsoperasjoner med rene senegraft. - Implantater som krever ben-innvekst (eks. usementert hofteprotese) - Andre frakturer og situasjoner med dårlige tilhelingsforhold for ortopediske strukturer eller hud, operatør skal da si spesielt ifra.

69 Anesth Analg Jul;105(1):19-20.

70 Non-steroidal anti-inflammatory drugs, cyclooxygenase-2 and the bone healing process. Vuolteenaho K, Moilanen T, Moilanen E. Basic Clin Pharmacol Toxicol Jan;102(1): Results of fracture healing studies in animals treated with NSAIDs or in mice lacking COX-2 gene show that inhibition or deficiency of COX-2 impairs the bone healing process. -The limited clinical data also support the assumption that inhibition of COX-2 by non-selective or COX-2-selective NSAIDs delays fracture healing. -However, the clinical significance of the effect in various patient groups needs to be carefully assessed and further investigations are needed to characterize the patients at the highest risk for NSAID-induced delayed fracture healing and its complications. - In the meantime, use of NSAIDs in fracture patients should be cautious, keeping in mind the benefits of pain relief and inhibition of ectopic bone formation on one hand, and the risks of non-union and retarded union on the other hand.

71

72 December 2007

73

74

75

76 Schweiz Med Wochenschr Nov 27;123(47): Links Fluor in the treatment of osteoporosis. An overview of thirty years clinical research. Dequeker J, Declerck K. Department of Rheumatology and Arthritis, K. U. Leuven, U. Z. Pellenberg, Belgium. t has long been known that fluoride "hardens" mineralized tissues. Fluoride ingestion through drinking water in areas naturally rich in fluoride leads to osteosclerosis, known as endemic fluorosis. The first suggestion that fluoride be used in the treatment of osteoporosis was made in However, despite 30 years of research, the treatment remains controversial. Fluoride has a dual effect on osteoblasts. On the one hand, it increases the birthrate of osteoblasts at tissue level by a mitogenic effect on precursors of osteoblasts, while on the other hand it has a toxic effect on the individual cell with mineralization impairment and reduced apposition rate resembling osteomalacia. Fluoride has a positive effect on axial bone density, but the axial bone gain is not matched by similar changes in cortical bone. Furthermore, approximately one third of patients are non-responders. The effect of the addition of fluoride to the drinking water on fracture rate is not clear. It probably only has a small relative impact on total hip fracture rates. In two controlled fluoride therapy studies the incidence of vertebral fractures decreased, while in two other studies it increased. Experience teaches that denser bones are not necessarily better bones. The major side effects of fluor therapy are skeletal fluorosis, gastrointestinal intolerance, and painful lower extremity syndrome. Fluoride is the single most effective agent for increasing axial bone volume in the osteoporotic skeleton; however, its therapeutic window is narrow. The best candidates for fluoride therapy are patients with axial osteoporosis but with good peripheral bone density. They should have a good renal function and vitamin D status.(abstract TRUNCATED AT 250 WORDS)

77 IKKE-PLANLAGT INNLEGGELSE OG RE- INNLEGGELSE (Ullevaal, 2411 patients): Grøgaard B, Aasbøe V, Ræder J. Tidsskr DNLF 1996:116:742-5 INNLEGGELSE: 1.5% (35 pasienter) kirurgi 37% anestesi 29% (inkl. kvalme) smerte 20% sosiale års. 14%

78 IKKE-PLANLAGT INNLEGGELSE OG RE- INNLEGGELSE (Ullevaal, 2411 patients): Grøgaard B, Aasbøe V, Ræder J. Tidsskr DNLF 1996:116:742-5 INNLEGGELSE: 1.5% (35 pasienter) kirurgi 37% anestesi 29% (inkl. kvalme) smerte 20% sosiale års. 14% RE-INNLEGGELSE*: 1.0% (24 pasienter) kirurgi 88% smerte 12%

79 ALL Hernia Anal Ost.r IN-HOSPITAL RECOVERY PERIODE % SMERTE (medium/mye), % I.V.OPIOID: Ost.t Knee OPIOID I.V. PAIN Dupuy Gangl Varic Ullevaal, data on file Cholec

80 IKKE-PLANLAGT INNLEGGELSE OG RE- INNLEGGELSE (Ullevaal, 2411 patients): Grøgaard B, Aasbøe V, Ræder J. Tidsskr DNLF 1996:116:742-5

81 Konsekvenser av smerte: Ubehag for pasienten Adrenerg respons Kardiovaskulært: BT stiger, Hjertefrekvens øker Redusert sirkulasjon (=funksjon) i nyre, tarm Generell stress respons Katabolisme Immobilisering Sekundære effekter: fysiske, psykiske, sosiale Økte sekundær kostnader Medikamenter, behandling, innlegging, sykemelding osv

82 Hvordan kan vi dempe smerten med medikamenter? Lokal anestesi Paracetamol NSAID Coxib (cox-ii spesifikke NSAID) Corticosteroider Spesielle Calcium blokkere (nevrogen smerte) Antikonvulsiva (nevrogen smerte) Opioider iv / (im) / oralt Epidural analgesi (ketamin)

83 CELLE traume PHOSFOLIPID phosfolipase ARACHIDONIC ACID Cyclo-oxygenase LEUKOTRIEN smerte inflammasjon allergi? PROSTAGLANDIN VEVS HOMEOSTASE nyrer GI-mucosa trombocyter smerte inflammasjon NSAID

84 CELLE traume PHOSFOLIPID phosfolipase CORTICO STEROID smerte inflammasjon LEUKOTRIEN smerte inflammasjon allergi? ARACHIDONIC ACID Cox-II Cyclo-oxygenase Cox-I? PROSTAGLANDIN VEVS HOMEOSTASE nyrer GI-mucosa trombocyter PROSTAGLANDIN NSAID COXIB substrate activator PARACETAMOL?

85 VEV (skade) LEUKOTRIENER FOSFOLIPID fosfolipase ARAKIDONSYRE PROSTAGLANDIN Cox-II Cyclo-oksygenase Cox-I STEROID Cox-2 hemmer PROSTAGLANDIN smerte inflammasjon tilheling? substrat aktivator PARACETAMOL smerte inflammasjon VEVSHOMEOSTASE nyrer GI-slimhinne trombocyter NSAID

86 COX-2 Upregulation Following Unilateral Hind-paw Inflammation Goppelt-Struebe. Recent advances in prostaglandin, and leukotriene research. Plenum Press, NY. 1998, pp

87 Glukokortikosteroider??

88 BETAMETHASONE 12 mg i.m. (B) vs. PLACEBO (P): (hemorrhoidectomy or big toe osteocynthesis) (mean ± SD) Group P(n=40) Group B(n=38) VAS 3 h: 32 ± ± 17 ** VAS 4 h: 28 ± ± 18 * Verbal Pain Score, 4-24 h post.op (0-3): 1.9 ± ±0.1 *** Nausea or vomiting 5-24 h (%): 38 % 11 % ** Satisfaction, 24 h (bad/medium/good): 9/9/22 1/5/30 ** * P<0.05, ** P<0.01, *** P< Aasbø V, Ræder JC, Grøgaard B. Anesth Analg 1998:87:319-23