Transcript Slide 1

Perioperative Pregabalin
Improves Postoperative
Outcomes after TKA
Asokumar Buvanendran, MD
Associate Professor
Director of Orthopedic Anesthesia
Department of Anesthesiology
Rush University Medical College
Chicago, IL
Co-Investigators:
J. Kroin, PhD
C. Dellavalle, MD (orthopedic surgery)
M. Kari, MD
M. Moric, PhD
K. Tuman, MD
Medical school grant from Pfizer
Voltage-Gated Calcium Channel
Structure
Mechanism of Analgesia
• Gabapentin and Pregabalin bind to the alpha-2-delta
sub-unit of the N-type voltage gated calcium channel
• Same mechanism of action whether it is neuropathic pain or inflammatory pain
(post-surgical)
• This binding results in ↓ release of
• Substance P, Calcitonin Gene-related peptide
• Glutamate
• Little effect on normal neuronal tissue, but only
effective in sensitized neuronal tissue
Pregabalin Binds to the 2- Subunit
of Voltage-Gated Ca2+ Channels in the Central
Nervous System
Pregabalin
Presynaptic
α2-
subunit
Ca2+
channel
Neurotransmitters
Presynaptic
α2-
subunit
Ca2+
channel
Neurotransmitters
Postsynaptic
Postsynaptic
Schematic representation of pregabalin’s proposed mechanism of action
• Pregabalin selectively binds to 2- subunit of calcium channels
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•
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Modulates calcium influx in hyperexcited neurons
Reduces neurotransmitter release
Pharmacologic effect requires binding at this site
The clinical significance of these observations in humans is currently unknown
Taylor. CNS Drug Rev. 2004;10:1832004;10:183-188.
Pregabalin and Postoperative Pain
• 3-5 RCT all show:
• ↓ pain scores
• Opioid sparing
• Doses used preop:
100-300 mg
• Doses used postop:
75-150 mg
Gilron I: Current opinion Anesthesiology 2007; 20: 456-472
RCT: Study Design (Level 1)
• 240 Patients randomized into 2 groups:
− Preop pregabalin 300 mg + Postop 150 mg BID for 10
days and then 75 mg BID and titrated to 50 mg and
stopped on day #14
− Preop Placebo + Postop Placebo
• Standard surgery and anesthesia
• Anesthesia:
−Combined spinal epidural
RCT: Study Design (Level 1)
• Outcomes:
−Standard postoperative epidural solution of
fentanyl + Bupivacaine:
• consumption titrated to VAS Acute Pain
−VAS Scores
−Sleep Interference
−ROM of the operated Knee:
• Active
• Passive
Demographics
Treatment group
Placebo
Pregabalin
120
120
Gender (M/F)
36/84
29/91
Years of Age
65 ± 9
67 ± 8
Weight (kg)
91 ± 26
85 ± 23
Height (cm)
169 ± 9
167 ± 9
Duration of surgery (min)
100.9 ± 31.7
108.6 ± 28.2
Tourniquet time (min)
86.2 ± 40.1
84.0 ± 33.6
190.4 ± 139.8
163.3 ± 147.1
2515 ± 742
2467 ± 616
Number
Blood loss (mL)
Total crystalloid (mL)
Results: Epidural Consumption
Epidural analgesic consumption over 24 hours was less in the pregabalin group versus placebo (P < 0.0001).
Results: ROM
Active ROM (P<0.001) was greater in the pregabalin group versus placebo.
Outcomes
• Passive ROM: Postop Day #2:
− Pregabalin:
− Placebo:
88.9  9.9
83.7  15.2 * P =0.012
• Sleep Interferance: Postop Day #1:
− Pregabalin:
− Placebo:
2.9  3.3
4.6  3.2 * P= 0.035
Incidence of Postoperative Adverse Events
Adverse event
Placebo
Pregabalin
P
Confusion
9
15
0.206
Dizziness
16
25
0.103
Sedation
28
35
0.344
Headache
0
2
0.146
Dry mouth
3
10
0.067
Peripheral edema
1
0
0.326
Double vision
0
2
0.147
Itching
13
6
0.110
Nausea
27
17
0.105
Vomiting
24
16
0.223
Conclusion
• The perioperative administration of Pregabalin
for TKA patients can lead to:
− ↓ Opioid consumption
− ↑ ROM of the operated Knee both passive and
active