Acute pain management gunadi bandung
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From clinical evidence to clinical practice
Reumatologi Klinik Bandung 2013
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Pain Pain – an unpleasant sensory & emotional experience associated with actual & potential tissue damage, or described in terms of such damage, or both.
(International Association for the Study of Pain)
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DescartesStimulus response model
Ascending pain
N +N
Spinal cord
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NociceptionNociception (noxious stimuli)
NeuropathicNeuropathic (functional abnormalities of the nervous system)
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LocationDurationFrequencyUnderlying causeIntensity
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• Acute pain –<30 days’ duration• Chronic pain - >6 months• Subacute pain – from the end of the
first month to the beginning of the seventh month of continued pain
• Recurrent acute pain – persists over an extended period of time but occurs mainly as isolated episodes
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➢ VAS=0->4
➢ VAS=4->7
➢ VAS>7
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Simple analgesia
Weak opioid
Potent opioid
Interventional Neural Blockade
+/- adjuvant
+/- adjuvant
+/- adjuvant
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• attempt to determine etiology of pain
• causative or symptomatic treatment
• the definitive cure of the pain syndrome
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• Patient interview– Pain history– Medical history– Drug history– Social history
• Patient examination– General
examination– Systems
examination
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• Goal of therapy – minimal pain & maximal function
• nonpharmacologic treatment options (kind words, a gentle touch, just being present)
• pharmacologic treatment
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Non OpioidsParacetamolNSAIDSCOX 2 inhibitors
OpioidsWeakStrong
NaloxoneNaloxone
Reumatologi Klinik Bandung 2013
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Acetaminophen (Paracetamol) Non-steroidal anti inflammatory
drugs (NSAIDS) COX 2 inhibitors
Reumatologi Klinik Bandung 2013
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Effects› Anti-inflammatory› Analgesic › Anti-pyretic › Anti-platelet
Reumatologi Klinik Bandung 2013
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COX 2 COX 2 INHIBITORSINHIBITORS
Celecoxib (Celebrex) Etoricoxib (Arcoxia) Parecoxib (Dynastat) Meloxicam ( Movicox)
NSAIDSNSAIDS Diclofenac
(Voltaren) Mefenamic Acid
(Ponstan) Ibuprofen ( Osdtarin) Naproxen (Gesiprox) Ketoprofen
(Kaltrofen, Profenide)
Ketorolac (Toradol)
Reumatologi Klinik Bandung 2013
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• sole treatment for mild to moderate pain
• adjunct to other analgesics for more severe pain
• for both acute & chronic pain
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Postoperative – Postoperative – mild to moderate painmild to moderate pain Orthopedic – acute low back pain1,2
Dental – periodontitis Oral surgery – 3rd molar surgery Gynecological – dysmenorrhea Urological – renal colic
2 Tulder et al. Non-steroidal anti-inflammatory drugs for low-back pain. The Cochrane Database of Systematic Reviews 2000, Issue 2. Art. No.: CD000396. DOI: 10.1002/14651858
1 Griffin et al. Do NSAIDs help in acute or chronic low back pain? Am Fam Physician 2002;65
Vimolluck Sanansilp, SirirajVimolluck Sanansilp, Siriraj
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Ceiling effect to analgesia Adverse effects
› Gastric ulceration› Reduction in renal blood flow › Platelet inhibition› Allergic reactions
Bronchospasm Cross allergy is common
Gastritis and functional thrombocytopenia are common with therapeutic doses
Precautions – prolonged use can lead to › Renal failure› Increased risk of myocardial infarct and stroke
Reumatologi Klinik Bandung 2013
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Pro
thro
mb
oti
cLess G
I sid
e e
ffect
Prostacyclin Inhibition ( COX-2 mediated )
Thromboxane Inhibition ( COX-1 mediated )
An
ti-thro
mb
otic
More
GI s
ide to
xic
ity
CelecoxibCelecoxibEtoricoxibEtoricoxib
DiclofenacDiclofenac IbuprofenIbuprofen ASAASA NaproxenNaproxen
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Drug : Class effect ?Individual properties ? :
DoseMolecule/ChemistryHalf-lifeEffect to BP & sodium
Duration of Rx
NoNo
Dose-related
YeYess
YeYessYeYessYeYess
YeYess
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ITT=intention-to-treat; NSAID=nonsteroidal anti-inflammatory drug.Adapted from Cannon CP, et al. Lancet. 2006;368:1771–1781.
34,701 patients randomized to treatment
5283 patients not randomized
39,984 patients screened
Etoricoxib 60 and 90 mg pooled17,412 started treatment
ITT Population
Not included in per protocol population
223 (1.3%) <75% compliant
388 (2.2%) took nonstudy
NSAID >10% of time
16,483 (95.3%)in per protocol population
Diclofenac 150 mg17,289 started treatment
ITT Population
Not included in per protocol population
463 (2.7%) <75% compliant
362 (2.1%) took nonstudy
NSAID >10% of time
16,819 (96.6%)in per protocol population
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CV=cardiovascular; PP=per protocol; CI=confidence interval; HR=hazard ratio.Adapted from Cannon CP, et al. Lancet. 2006;368:1771–1781.
Cum
ulat
ive
Inci
denc
e,
% (
95%
CI)
Months
0 6 4224
Etoricoxib 60 and 90 mg pooled (320 events)Diclofenac 150 mg (323 events)
7
0
Patients at risk Etoricoxib 16,819 13,359 10,733 8277 6427 4024 805 Diclofenac 16,483 12,800 10,142 7901 6213 3832 815
12 18 30 36
6
5
4
3
2
1
Etoricoxib vs diclofenacHR=0.95 (95% CI: 0.81, 1.11)
P=0.496
Primary End Point
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mITT (14 Days) Analysis
In Patients With RA
Etoricoxib 90 mg RADiclofenac 150 mg RA
mITT=modified intention-to-treat; OA=osteoarthritis; RA=rheumatoid arthritis; SE=standard error; BL=baseline.aFor etoricoxib 60 mg cohort.bFor etoricoxib 90 mg cohort.
Mea
n C
han
ge ±
SE
15
10
0
–0.5
BL 4 8 12 16 20 24 28 32 36
Months
5
1
In Patients With OA
Mea
n C
han
ge ±
SE
15
10
0
–0.5
Etoricoxib 60 mg OADiclofenac 150 mg OAa Etoricoxib 90 mg OADiclofenac 150 mg OAb
BL 4 8 12 16 20 24 28 32 36
Months
5
1
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Pat
ient
s, %
Osteoarthritis
60 mg vs Diclofenac 90 mg vs Diclofenac 90 mg vs Diclofenac
Rheumatoid Arthritis
mITT (14 Days) Analysis
mITT=modified intention-to-treat; CI=confidence interval.aDifference in proportions (95% CI).
EtoricoxibDiclofenac 150 mg
P=0.027
P<0.001 P=0.030
2.16
2.53 2.43
1.63
1.11
1.61
0.0
0.5
1.5
2.5
3.0
1.0
2.0
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Patients at risk for upper GI events, no. Etoricoxib 17,412 13,704 10,972 8400 6509 4063 821 Diclofenac 17,289 13,190 10,396 8027 6306 3867 820
Cum
ulat
ive
Inci
denc
e,
% (
95%
CI)
Months
0 6 4224
3.0
0
12 18 30 36
2.5
2.0
1.5
1.0
0.5
Etoricoxib 60 and 90 mg pooled (176 events)Diclofenac 150 mg (246 events)
Etoricoxib vs diclofenacHR=0.69 (95% CI: 0.57, 0.83)
GI=gastrointestinal; ITT=intention-to-treat; CI=confidence interval; HR=hazard ratio.aThese included uncomplicated (perforation, ulcer, and bleeds) and complicated (perforation, obstruction, and bleeds) events.Adapted from Laine L, et al. Lancet. 2007;369:465–473; Cannon CP, et al. Lancet. 2006;368:1771–1781.
All confirmedeventsa
P=0.0001
P=0.561
Complicatedevents
Etoricoxib vs diclofenacHR=0.91 (95% CI: 0.67, 1.24)
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P=0.696
P=0.284
P=0.895
0.07(–0.24, 0.37)a
0.50 (–0.36, 1.37)a
0.04 (–0.49, 0.57)a
0.81
2.30
1.02
0.75
1.80
0.98Pat
ient
s, %
60 mg vs Diclofenac 90 mg vs Diclofenac
mITT (14 Days) Analysis
mITT=modified intention-to-treat; CI=confidence interval.aDifference in proportions (95% CI).
0.0
0.5
1.5
2.5
3.0
1.0
2.0
90 mg vs Diclofenac
EtoricoxibDiclofenac 150 mg
Osteoarthritis Rheumatoid Arthritis
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GI=gastrointestinal; AEs=adverse events; mITT=modified intention-to-treat; PY=patient-years; OA=osteoarthritis; RA=rheumatoid arthritis; COX=cyclooxygenase.aEvents within 1 year of treatment; bFor both COX proportion hazard and stratified log-rank test.
P<0.001b
P<0.001b
P<0.001b
3.79
8.20
4.15
6.83
12.56
7.42
0
5
10
15
20
Ra
te/1
00
PY
Etoricoxib Diclofenac 150 mg
60 mg/day vsDiclofenac
90 mg/day vsDiclofenac
90 mg/day vsDiclofenac
Patients With RAPatients With OA
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Is an NSAID needed ? Inflammation ?
Use non-pharmacologic or other pharmacologic Rx
Is there a contraindication to NSAID ? - Renal insufficiency ( CrCl < 30 ) - Allergic reaction - Concurrent GI injury
No Yes
Yes
No
Is there a reason that a classical NSAID cannot be used ?- GI risk+ & Bleeding risk
YesNo
Use classical NSAID Use COX-2 inhibitor ( or classical NSAID + PPI+)
Is patient at increased risk for CV events ?
Select NSAID on the basis of GI risk Avoid NSAID esp. COX-2 inhibitor
No Yes
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32Reumatologi Klinik Bandung 2013
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