Hyperalgesia, Secondary
Conditions
Keywords
postoperative, hyperalgesia, pain, transversus abdominis plane block, TAP block, cesarean section
Brief summary
The purpose of this study is to determine whether a transversus abdominis plane (TAP) block with Clonidine added to the injectate (Clo-TAP) performed approximately 2hrs after the cesarean section (CS) will decrease the amount of postoperative hyperalgesia and ultimately reduce post-CS chronic pain.
Detailed description
Acute severe pain after cesarean section (CS) occurs more often than is thought and 10-15% of the women having a cesarean section develop chronic pain (Kehlet et al. 2006). With over 1.3 million cesarean deliveries per year in the US, this is bound to create a significant health problem. One way to address this health burden is to refine techniques that may help control the pain women experience after CS and ultimately reduce the potential to develop chronic pain. The purpose of this randomized, double-blinded study is to evaluate the ability of an established anesthetic technique called the transversus abdominis plane (TAP) block to reduce the amount of hyperalgesia women develop around their incision after CS. Measuring the amount of punctuate mechanical hyperalgesia is used as a tool to assess postoperative central sensitization (Lavand'homme et al. 2005), which contributes to postoperative acute pain. Since postoperative acute pain has been shown to be predictive of developing postoperative chronic pain (Eisenach et al. 2008; Yarnitsky et al. 2008), an effective TAP block could help diminish the incidence of chronic pain after CS. In addition, blood samples will be collected for future genetic analysis and we will test preoperatively for mechanical temporal summation (mTS) to evaluate CNS (central nervous system) sensitization and nociceptive system hyperexcitability and see if this correlates with the amount of hyperalgesia women develop around their incision after surgery. The primary aim of this study is to evaluate the benefits of two different solutions injected by TAP block technique on postoperative peri-incisional hyperalgesia.
Interventions
DRUGBupivacaine Placebo
2 x 20mL 0.9% NaCl
2 x 1mL 0.9% NaCl
DRUGBupivacaine
2 x 20mL 0.375% Bupivacaine = 150 mg Bupivacaine
DRUGClonidine
2 x 1ml Clonidine = 150 µg Clonidine
Sponsors
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* non-laboring women who will benefit from and have clinically consented to a scheduled or non-scheduled cesarean delivery under spinal anesthesia * English speaking (UW Site) or Portuguese speaking (Brazil site) * aged between 18 and 45 years * BMI \< 40 * ASA physical status class I or II
Exclusion criteria
* laboring women undergoing a non-scheduled cesarean delivery * non-English speaking (UW Site) or non-Portuguese speaking (Brazil site) * previous spinal surgery * contraindications for neuraxial anesthesia * allergy to local anesthetic, ultrasound conduction gel, or Clonidine * history of chronic pain * inability to receive intraoperative Toradol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Wound Hyperalgesia Index (WHA) Assessed 48 Hrs After Block Placement in the Different Groups | 48hrs after CS | Determine which of three different TAP formulations (Placebo, TAP, Clo-TAP) has the most beneficial effect on the postoperative area of hyperalgesia 48hrs after the start of the cesarean section. The smaller the area of WHA, assessed in cm2, the better the outcome. Area sizes may range from 0 to any size. |
Countries
Brazil, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Sterile Saline used for TAP block = Bupivacaine Placebo + Clonidine Placebo
Bupivacaine Placebo: 2 x 20mL 0.9% NaCl
Clonidine Placebo: 2 x 1mL 0.9% NaCl | 30 |
| TAP (Bupi) 2x20mL 0.375% Bupivacaine + 2x1mL of 0.9% NaCl = 150mg Bupivacaine + Clonidine Placebo
Clonidine Placebo: 2 x 1mL 0.9% NaCl
Bupivacaine: 2 x 20mL 0.375% Bupivacaine = 150 mg Bupivacaine | 30 |
| Clo-TAP (Bupi + Clon) 2x20mL 0.375% Bupivacaine + 2x1mL Clonidine = 150mg Bupivacaine + 150µg Clonidine
Bupivacaine: 2 x 20mL 0.375% Bupivacaine = 150 mg Bupivacaine
Clonidine: 2 x 1ml Clonidine = 150 µg Clonidine | 30 |
| Total | 90 |
Baseline characteristics
| Characteristic | Placebo | TAP (Bupi) | Clo-TAP (Bupi + Clon) | Total |
|---|---|---|---|---|
| Age, Continuous | 30.5 years STANDARD_DEVIATION 6.7 | 31.8 years STANDARD_DEVIATION 4.5 | 29.5 years STANDARD_DEVIATION 6.7 | 30 years STANDARD_DEVIATION 5.5 |
| Sex: Female, Male Female | 30 Participants | 30 Participants | 30 Participants | 90 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 30 | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 | 0 / 30 |
Outcome results
Primary
Wound Hyperalgesia Index (WHA) Assessed 48 Hrs After Block Placement in the Different Groups
Determine which of three different TAP formulations (Placebo, TAP, Clo-TAP) has the most beneficial effect on the postoperative area of hyperalgesia 48hrs after the start of the cesarean section. The smaller the area of WHA, assessed in cm2, the better the outcome. Area sizes may range from 0 to any size.
Time frame: 48hrs after CS
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Wound Hyperalgesia Index (WHA) Assessed 48 Hrs After Block Placement in the Different Groups | 1.07 cm^2 |
| TAP (Bupi) | Wound Hyperalgesia Index (WHA) Assessed 48 Hrs After Block Placement in the Different Groups | 1.27 cm^2 |
| Clo-TAP (Bupi + Clon) | Wound Hyperalgesia Index (WHA) Assessed 48 Hrs After Block Placement in the Different Groups | 0.74 cm^2 |
Comparison: We estimated that 25 subjects per group would allow us to detect a reduction of this area from 7.5 cm2 in our placebo group to 3.5 cm2 in the CloTAP group, with SD = 5 cm2 in both groups, owing to improved overall analgesia and reduced pain sensitization in women allocated to receive a TAP block with clonidine (2-tailed \[alpha\] = 0.05, 80% power). To allow for failed TAP blocks and/or exclusions of cases, we included 30 patients per group (n = 90)p-value: 0.48ANOVA