Statistical modeling in pharmaceutical research and development.
Â
Management of acute postoperative pain r
1.
2. What is Pain?
âPain is an unpleasant sensory and emotional
experience associated with actual or potential
tissue damage or described in terms of such
damage.â
International Association for the Study of Pain, 1979
3. ACUTE PAIN
Most common forms:
⢠Posttraumatic
⢠Postoperative
⢠Obstetric pain
⢠Pain associated with acute medical illnesses
4. Pain: The 5th Vital Sign
1. Temperature
2. Blood Pressure
3. Pulse
4. Respiratory Rate
American Pain Society. 1998
5. Pain Assessment
6. SELF-REPORT SCALES
âGOLD STANDARDâ
Manne et al Pain 1992
McGrath et al Pain 1996
Chambers et al Pain 1999
Soetenga et al Pediatric Nursing 1999
Voepel-Lewis et al Anesthesia and Analgesia 2002
Willis et al Pediatric Nursing 2003
14. PREEMPTIVE ANALGESIA
âAn antinociceptive therapy that prevents
establishment of altered processing of
afferent input, which amplifies postoperative
painâ
Kissin, I. Preemptive Analgesia. Anesthesiology 2000;93(4):1138-1143)
15. Preemptive analgesia
aims to stop pain before even it begins
preemptive
analgesia
receptor
sensitization
pain
stimulus
16. PREEMPTIVE ANALGESIA
⢠fundamental principles:
(a) that the central nervous system is capable
of changing so that pain becomes either
improved or worsened via central processes
such as desensitization and sensitization
(b) that alterations in sensory and pain
transmission can effect such changes
17. OPIOID SPARING & MULTIMODAL ANALGESIA
Current teaching states that good pain relief during and
after surgery, using opioids whenever necessary, can
improve surgical recovery.
Carr DB, Goudas LC. Acute pain. Lancet. 1999; 362(9169):2051-2058
Pain relief is an important component of accelerated
recovery programs that aim to achieve early return
of mobility, coughing, and bowel and bladder
function, and to restore normal physiologic
functioning as rapidly as possible, thereby reducing
complication rates.
Brennan TJ, Kehlet H. Preventive analgesia to reduce wound hyperalgersia and persistent postsurgical pain. Not an easy path.
Anesthesiology 2005;103:681-683
18. OPIOID SPARING AND MULTIMODAL ANALGESIA
OPIOIDS
most effective
analgesics
sedating
nauseating
slows bowel activity
delay recovery
20. TREATMENT OPTIONS
Opioids
⢠mainstay of acute pain treatment
⢠used alone or in combination with other
analgesics
⢠higher doses of parenteral opioids are given
during the first 24-48 hours after surgery
⢠IV route is preferred
SYSTEMIC TREATMENTS
22. Choice of opioids
Morphine
⢠the standard, most widely used
⢠least lipophilic opioid
â delayed peak effect (occurs at 20 minutes after IV injection)
⢠highly metabolized
â morphine-6-glucoronide
â morphine-3-glucoronide
⢠induces histamine release
⢠duration of a standard dose (10mg) = 3-4 hrs
⢠poor oral bioavailability, (oral dose is 3x parenteral dose)
⢠may cause biliary and urinary tract spasm
25. NSAIDs and ACETAMINOPHEN
Acetaminophen
⢠not strictly an anti-inflammatory drug, but
shares many of the properties of NSAIDs
⢠acidic and crosses the blood-brain barrier
⢠action resides mainly in the central nervous
system
â prostaglandin inhibition produces analgesia and
antipyresis
26. NSAIDs and ACETAMINOPHEN
Ketorolac
⢠first injectable NSAID approved for
use surgical patients
⢠potent NSAID
⢠side-effect profile reflects its potency
28. Adverse Effects and Limitations on
Perioperative Use of NSAIDs
⢠GI hemorrhage
⢠Renal dysfunction
⢠Decreased hemostasis
⢠Asthma (in susceptible individuals)
⢠Anaphylaxis
29. Adverse Effects and Limitations on
Perioperative Use of NSAIDs
Contraindications to NSAID use:
âHistory of peptic ulcer disease
âHistory of intolerance to NSAIDs
âRenal failure, renal dysfunction
âOld age
30. Acetaminophen
â relatively safe
â not associated with the adverse effects listed for
standard NSAIDs.
COX-2 inhibitors
â less likely to cause bleeding
â b carry the same risk as standard NSAIDs of the
other listed adverse effects
â cardiovascular and thrombotic risks
31. NSAIDs safe for perioperative use?
ďźused for a short period
ďźmost adverse effects associated with
prolonged use
32. Use of NSAIDs and ACETAMINOPHEN
for POSTOPERATIVE PAIN
⢠for mild postoperative pain
⢠as adjuncts in multimodal analgesia
â 30-50% opioid-sparing effect
â 30% reduction in nausea
â 29% reduction in sedation
34. The Inherent Safety of PCA
⢠dosing regiments == small frequent doses
⢠avoid the large swings between peaks and
lows associated with less frequent and
larger doses
⢠a single dose is too small to produce overt
sedation or respiratory depression
⢠less need for monitoring
35. Benefits of PCA
Meta-analyses of PCA vs conventional analgesia:
⢠slightly better analgesia associated with PCA
use
⢠large difference in patient satisfaction favoring
PCA,
⢠no difference in opioid usage, side effects, or
surgical outcome
36. Patient-Controlled Epidural Analgesia
⢠PCA technology can also be used for epidural
analgesia
⢠main advantage is that patients like the sense
of control offered by the patient triggered
pump
37. SPECIAL POPULATIONS
⢠tolerate opioid poorly
â prone to apnea
â slow conjugation by liver
⢠smaller, more frequent dosing
⢠opioids ď mainstay for treating severe pain
â reduce opioid requirements
â use adjunctive treatments such as NSAIDs and
acetaminophen
⢠dosing is calculated on a per-kilogram basis
⢠frequent checking of vital signs mandatory
⢠use respiratory rate and oxygen saturation monitors
Neonates, Infants, and Children
38. The Elderly
⢠sensitive to opioids
â respiratory depressant effects
â central dysphoric and euphoric effects
⢠opioid-induced confusion is common
⢠sensitive to NSAID side effects
SPECIAL POPULATIONS