Continuous TAP Blocks: Relative Effects of a Basal Infusion vs. Repeated Bolus Doses
| Status: | Recruiting |
|---|---|
| Conditions: | Post-Surgical Pain |
| Therapuetic Areas: | Musculoskeletal |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | February 2016 |
| End Date: | June 2016 |
| Contact: | Brian Ilfeld, MD, MS |
| Email: | bilfeld@ucsd.edu |
| Phone: | 858-444-5949 |
Continuous Transversus Abdominis Plane Nerve Blocks: Relative Effects of a Basal Infusion vs. Repeated Bolus Doses (A Randomized, Double-Masked, Active-Control, Split-Body, Crossover Study)
Single-injection transversus abdominis plane (TAP) blocks have been used to treat
postoperative pain, and are become very popular within the United States because of their
high analgesic potency and relative ease of placement. Unfortunately, the longest local
anesthetic available lasts only 8-12 hours. Continuous TAP blocks—also termed "perineural
infusion"—involve bathing the multiple nerves of the abdominal wall in local anesthetic
using a percutaneously-inserted perineural catheter inserted just anterior (ventral) and
cephalad to the anterior superior iliac spine. For most catheter locations, an infusion is
preferred to a single-injection nerve block because the duration of analgesia may be
extended to better match the duration of surgical pain. But, unlike brachial plexus,
femoral, and sciatic nerve perineural infusion, a continuous basal infusion of local
anesthetic does not provide adequate analgesia for TAP catheters. This may be due to the
fact that the TAP is a relatively tight space, so it might require a bolus of fluid to
adequately spread the perineural local anesthetic to the multiple required nerves (as
evidence of this, single-injection TAP blocks are very effective, although with a limited
duration). The result is that while single-injection TAP blocks are widely used, TAP
catheters have not been adopted. This scenario leaves surgical pain untreated following the
resolution of the single-injection TAP block. The recent development of an infusion pump
that can automatically deliver repeated bolus doses may allow the spread of local anesthetic
to the multiple sensory nerves necessary to provide adequate analgesia, with a duration that
better matches postoperative requirements. The investigators therefore propose a randomized,
double-masked, controlled trial to determine if delivering local anesthetic as a repeated
bolus dose results in improved local anesthetic spread/effects compared with a continuous
basal infusion for TAP catheters.
postoperative pain, and are become very popular within the United States because of their
high analgesic potency and relative ease of placement. Unfortunately, the longest local
anesthetic available lasts only 8-12 hours. Continuous TAP blocks—also termed "perineural
infusion"—involve bathing the multiple nerves of the abdominal wall in local anesthetic
using a percutaneously-inserted perineural catheter inserted just anterior (ventral) and
cephalad to the anterior superior iliac spine. For most catheter locations, an infusion is
preferred to a single-injection nerve block because the duration of analgesia may be
extended to better match the duration of surgical pain. But, unlike brachial plexus,
femoral, and sciatic nerve perineural infusion, a continuous basal infusion of local
anesthetic does not provide adequate analgesia for TAP catheters. This may be due to the
fact that the TAP is a relatively tight space, so it might require a bolus of fluid to
adequately spread the perineural local anesthetic to the multiple required nerves (as
evidence of this, single-injection TAP blocks are very effective, although with a limited
duration). The result is that while single-injection TAP blocks are widely used, TAP
catheters have not been adopted. This scenario leaves surgical pain untreated following the
resolution of the single-injection TAP block. The recent development of an infusion pump
that can automatically deliver repeated bolus doses may allow the spread of local anesthetic
to the multiple sensory nerves necessary to provide adequate analgesia, with a duration that
better matches postoperative requirements. The investigators therefore propose a randomized,
double-masked, controlled trial to determine if delivering local anesthetic as a repeated
bolus dose results in improved local anesthetic spread/effects compared with a continuous
basal infusion for TAP catheters.
This investigation will be a randomized, observer-masked, controlled, split-body,
human-subjects clinical trial. Of note, the investigators will be using standard-of-care
local anesthetics under their FDA approved purpose and do not plan to research a possible
change of indication or use of these drugs as part of this research project.
Volunteers will be solicited using the CTRI Research Match and an existing database of
volunteers (IRB approved). If a volunteer meets inclusion/exclusion criteria (see
Eligibility Criteria) and desires study participation, written, informed consent will be
obtained using a UCSD IRB-approved/stamped ICF. A urine pregnancy test will be administered
to all women of childbearing age following written informed consent but before any study
interventions. This urine test will be administered by CTRI nursing staff using standard,
FDA-approved urine pregnancy testing devices.
Perineural catheter insertion: Following written, informed consent, subjects will be
admitted to the UCSD CTRI Center for Clinical Research Services (CCR) and have
demographic/morphometric data recorded (e.g., age, weight, height). An intravenous line will
be placed in an upper extremity, followed by external monitors (pulse oximeter, blood
pressure, and EKG), and oxygen by nasal cannula. Sedation will be provided with intravenous
fentanyl (50 μg) and/or midazolam (1 mg). Bilateral TAP perineural catheters (FlexBlock,
Teleflex Medical, Reading, PA, USA) will be inserted using ultrasound guidance using a
technique previously described. To check the perineural catheter placement accuracy, 5 mL of
normal saline will be administered via the catheters under ultrasound guidance with the
definition of a successful catheter insertion an increase in fluid volume within the TAP
(the plane between the transversus abdominis muscle and internal oblique muscle).
Inaccurately inserted catheters will be replaced.
Treatment Group Assignment: Subjects will act as their own controls: the right side will be
randomized to one of two treatment groups: ropivacaine 0.2% administration as either a basal
infusion (8 mL/h) or bolus doses (24 mL administered every 3 hours). The left side will
receive the other possible treatment. Randomization will be based on computer-generated
codes. Randomization will be in blocks of four. An infusion pump with study infusate will be
attached to each of the perineural catheters and initiated at Hour 0. The basal rate and
bolus volume will depend upon the treatment group (note that the basal rate and bolus volume
differ for each treatment group, but the total dose of local anesthetic is the same for
each):
The tubing from the pumps to the subjects will be gently wound at least 5 rotations and
covered with opaque tape, masking which perineural catheter is receiving which treatment
(ropivacaine is clear, so the flow through the clear tubing from the tape to the perineural
catheters will not be visually distinguishable).
Local Anesthetic Administration: The infusion pump administering the basal infusion will be
initiated at Hour 0. The infusion pump administering bolus doses will administer a 24 mL
bolus dose every 3 hours beginning at Hour 0. Perineural catheters will be removed after 6
hours (a total of 2 bolus doses).
Food and Drink: Both food and accompanying beverages/water will be provided by the hospital
and served by the nursing staff immediately following catheter insertion. Meals will be
provided without charge to the study subjects. There is no restriction on oral intake
following catheter insertion. Subjects will remain within the CTRI-CCR until catheter
withdrawal.
Outcome measurements: At all time points, the right side will be measured first, followed by
the left side (subjects in the supine position).
Measurements will be performed at baseline (prior to local anesthetic administration), after
6 hours of administration, and at each hour in between for a total of 7 time points:
- Hour 0 (baseline) just prior to local anesthetic administration
- Hours 1 and 2
- Hour 3, just prior to the scheduled bolus dose at Hour 3
- Hours 4 and 5
- Hour 6
The sensory deficit will be measured using two methods:
- von Frey filaments (mechanical detection threshold)
- Cold roller (cold deficit)
The sensory deficit will be measured along two separate anatomical lines at each time point:
- The mid-axillary "vertical" line (measuring cephalad-caudad effects)
- A transverse "horizontal" line passing through the anterior superior iliac spine
(measuring anterior-posterior effects)
Statistical analysis: The investigators' calculations are focused on the primary hypothesis
that when using transversus abdominis plane (TAP) block perineural catheters, providing
local anesthetic in repeated bolus doses increases the cephalad-caudad local anesthetic
effects compared with a basal-only infusion of the same volume and dose of local anesthetic.
To measure cephalad-caudad local anesthetic effects, we will measure the cephalad-caudad
sensory deficit to cold temperature in centimeters along the mid-axillary line. The primary
end point will be this measurement after 6 hours of local anesthetic administration (6 hours
of a continuous basal infusion or 2 bolus doses at 3-hour increments, the last being 3 hours
prior to the measurement of the primary endpoint). Each subject will act as their own
control with each side receiving a different treatment. Normality of distribution will be
determined using the Shapiro-Wilk normality test (Prism 6, GraphPad, San Diego, California).
For normally distributed data, comparisons for parametric and nonparametric data will be
tested using the t-test or Mann-Whitney test and presented as mean (SD) or median
[interquartile], respectively. Nominal data will be analyzed using the Pearson Chi square
test. P<0.05 will be considered significant.
Sample size estimation: With 21 evaluable subjects we will have 80% power at the 0.05
significance level to detect the superiority of the administration of local anesthetic as
repeated bolus doses as compared with a continuous basal infusion at Hour 6 (primary
outcome). Using an expected standard deviation of 7 cm for the primary endpoint, and given a
2-sided Type I error protection of 0.05 and power=0.80, approximately 21 subjects in each
treatment arm will be required to detect a difference between treatment group means of 6 cm.
Since this is a split-body study design and each subject will have one of each treatments on
opposite sides of the body, 21 subjects total will produce 21 subjects in each treatment
arm. The investigators chose 6 cm as a detectable treatment difference because a 3 cm
distance is approximately equivalent to the width of one dermatome, and the vast majority of
anesthesiologists would consider a 2-dermatome difference clinically significant. To allow
for a larger-than-anticipated standard deviations, smaller-than-anticipated difference
between treatment means, drop out subjects, or failed catheters, the investigators will
enroll a total of 24 subjects.
human-subjects clinical trial. Of note, the investigators will be using standard-of-care
local anesthetics under their FDA approved purpose and do not plan to research a possible
change of indication or use of these drugs as part of this research project.
Volunteers will be solicited using the CTRI Research Match and an existing database of
volunteers (IRB approved). If a volunteer meets inclusion/exclusion criteria (see
Eligibility Criteria) and desires study participation, written, informed consent will be
obtained using a UCSD IRB-approved/stamped ICF. A urine pregnancy test will be administered
to all women of childbearing age following written informed consent but before any study
interventions. This urine test will be administered by CTRI nursing staff using standard,
FDA-approved urine pregnancy testing devices.
Perineural catheter insertion: Following written, informed consent, subjects will be
admitted to the UCSD CTRI Center for Clinical Research Services (CCR) and have
demographic/morphometric data recorded (e.g., age, weight, height). An intravenous line will
be placed in an upper extremity, followed by external monitors (pulse oximeter, blood
pressure, and EKG), and oxygen by nasal cannula. Sedation will be provided with intravenous
fentanyl (50 μg) and/or midazolam (1 mg). Bilateral TAP perineural catheters (FlexBlock,
Teleflex Medical, Reading, PA, USA) will be inserted using ultrasound guidance using a
technique previously described. To check the perineural catheter placement accuracy, 5 mL of
normal saline will be administered via the catheters under ultrasound guidance with the
definition of a successful catheter insertion an increase in fluid volume within the TAP
(the plane between the transversus abdominis muscle and internal oblique muscle).
Inaccurately inserted catheters will be replaced.
Treatment Group Assignment: Subjects will act as their own controls: the right side will be
randomized to one of two treatment groups: ropivacaine 0.2% administration as either a basal
infusion (8 mL/h) or bolus doses (24 mL administered every 3 hours). The left side will
receive the other possible treatment. Randomization will be based on computer-generated
codes. Randomization will be in blocks of four. An infusion pump with study infusate will be
attached to each of the perineural catheters and initiated at Hour 0. The basal rate and
bolus volume will depend upon the treatment group (note that the basal rate and bolus volume
differ for each treatment group, but the total dose of local anesthetic is the same for
each):
The tubing from the pumps to the subjects will be gently wound at least 5 rotations and
covered with opaque tape, masking which perineural catheter is receiving which treatment
(ropivacaine is clear, so the flow through the clear tubing from the tape to the perineural
catheters will not be visually distinguishable).
Local Anesthetic Administration: The infusion pump administering the basal infusion will be
initiated at Hour 0. The infusion pump administering bolus doses will administer a 24 mL
bolus dose every 3 hours beginning at Hour 0. Perineural catheters will be removed after 6
hours (a total of 2 bolus doses).
Food and Drink: Both food and accompanying beverages/water will be provided by the hospital
and served by the nursing staff immediately following catheter insertion. Meals will be
provided without charge to the study subjects. There is no restriction on oral intake
following catheter insertion. Subjects will remain within the CTRI-CCR until catheter
withdrawal.
Outcome measurements: At all time points, the right side will be measured first, followed by
the left side (subjects in the supine position).
Measurements will be performed at baseline (prior to local anesthetic administration), after
6 hours of administration, and at each hour in between for a total of 7 time points:
- Hour 0 (baseline) just prior to local anesthetic administration
- Hours 1 and 2
- Hour 3, just prior to the scheduled bolus dose at Hour 3
- Hours 4 and 5
- Hour 6
The sensory deficit will be measured using two methods:
- von Frey filaments (mechanical detection threshold)
- Cold roller (cold deficit)
The sensory deficit will be measured along two separate anatomical lines at each time point:
- The mid-axillary "vertical" line (measuring cephalad-caudad effects)
- A transverse "horizontal" line passing through the anterior superior iliac spine
(measuring anterior-posterior effects)
Statistical analysis: The investigators' calculations are focused on the primary hypothesis
that when using transversus abdominis plane (TAP) block perineural catheters, providing
local anesthetic in repeated bolus doses increases the cephalad-caudad local anesthetic
effects compared with a basal-only infusion of the same volume and dose of local anesthetic.
To measure cephalad-caudad local anesthetic effects, we will measure the cephalad-caudad
sensory deficit to cold temperature in centimeters along the mid-axillary line. The primary
end point will be this measurement after 6 hours of local anesthetic administration (6 hours
of a continuous basal infusion or 2 bolus doses at 3-hour increments, the last being 3 hours
prior to the measurement of the primary endpoint). Each subject will act as their own
control with each side receiving a different treatment. Normality of distribution will be
determined using the Shapiro-Wilk normality test (Prism 6, GraphPad, San Diego, California).
For normally distributed data, comparisons for parametric and nonparametric data will be
tested using the t-test or Mann-Whitney test and presented as mean (SD) or median
[interquartile], respectively. Nominal data will be analyzed using the Pearson Chi square
test. P<0.05 will be considered significant.
Sample size estimation: With 21 evaluable subjects we will have 80% power at the 0.05
significance level to detect the superiority of the administration of local anesthetic as
repeated bolus doses as compared with a continuous basal infusion at Hour 6 (primary
outcome). Using an expected standard deviation of 7 cm for the primary endpoint, and given a
2-sided Type I error protection of 0.05 and power=0.80, approximately 21 subjects in each
treatment arm will be required to detect a difference between treatment group means of 6 cm.
Since this is a split-body study design and each subject will have one of each treatments on
opposite sides of the body, 21 subjects total will produce 21 subjects in each treatment
arm. The investigators chose 6 cm as a detectable treatment difference because a 3 cm
distance is approximately equivalent to the width of one dermatome, and the vast majority of
anesthesiologists would consider a 2-dermatome difference clinically significant. To allow
for a larger-than-anticipated standard deviations, smaller-than-anticipated difference
between treatment means, drop out subjects, or failed catheters, the investigators will
enroll a total of 24 subjects.
Inclusion Criteria:
1. healthy volunteers weighing more than 45 kg;
2. must be willing to have bilateral transverses abdominis plane nerve block catheters
be placed with subsequent ropivacaine administration and sensory testing for 6 hours
Exclusion Criteria:
1. BMI greater than 40 (BMI=weight in kg/ [height in meters];
2. regular opioid use within the previous 2 months;
3. previous participation within the same study;
4. allergy to study medications;
5. known renal insufficiency (creatinine > 1.5 mg/dL);
6. pregnancy;
7. incarceration; and
8. any known neuro-muscular deficit of either abdominal wall.
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