Effects of Catheter Location on Postoperative Analgesia for Continuous Adductor Canal and Popliteal-Sciatic Nerve Blocks

This will be a single-center (UCSD), randomized, controlled investigation.

Enrollment. Consenting adults undergoing knee arthroplasty or foot/ankle surgery with a
planned adductor canal or popliteal perineural catheter, respectively, will be offered
enrollment. Study inclusion will be proposed to eligible patients prior to surgery. If a
patient desires study participation, written, informed consent will be obtained using a
current UCSD IRB-approved ICF. Selection for inclusion will not be based on gender, race, or
socioeconomic status. Inclusion and exclusion criteria are listed in section #10 below.

Following written, informed consent, The Investigators will record baseline anthropomorphic
information (age, sex, height, and weight) that is already provided by all patients having
surgery. All subjects will have a peripheral intravenous (IV) catheter inserted, standard
noninvasive monitors applied, supplemental oxygen administered via a nasal cannula or face
mask, and positioned supine (adductor canal) or prone (popliteal-sciatic). Midazolam and
fentanyl (IV) will be titrated for patient comfort, while ensuring that patients remain
responsive to verbal cues. The area that will be subsequently covered by the catheter
dressing will be clipped of hair, if necessary. The ultrasound will be placed to visualize
the short axis (cross-section) of the adductor canal or popliteal regional at both proximal
and distal locations. If both sites are acceptable for catheter insertion, the subject will
be randomized using a computer-generated list (blocks of 8) to one of two treatment groups in
a 1:1 ratio using sealed, opaque, consecutively numbered envelopes stratified by catheter
type (adductor canal vs. popliteal-sciatic): (1) proximal vs (2) distal insertion.

Catheter insertion. Catheter insertion will adhere to current UCSD standard-of-care. The only
difference for subjects participating in the study (vs those not participating) will be that
the specific catheter insertion location—both currently standard-of-care and used daily at
UCSD because of clinical equipoise—will be determined randomly, instead of the physician
simply choosing him/herself. All catheters will be placed by a regional anesthesia fellow or
resident under the direct supervision and guidance of a regional anesthesia attending (or by
the attending him/herself). All catheters will be placed using standard UCSD perineural
catheter techniques, nerve in short-axis, ultrasound-guidance.

The area of insertion will be cleaned with chlorhexidine gluconate and isopropyl alcohol
(ChloraPrep One-Step, Medi-Flex Hospital Products, Inc., Overland Park, KS, USA), and a
clear, sterile, fenestrated drape applied. The ultrasound probe will be placed to visualize
the short-axis (cross-section) of the target nerve(s). A skin wheal will be raised at the
catheter-placement needle's anticipated point of entry (proximal or distal location). A 17
gauge needle (FlexTip, Teleflex Medical, Triangle Research Park, NC, USA) will be used to
place all perineural catheters. The catheter-placement needle will be inserted through the
skin wheal, advanced in-plane beneath the US transducer and directed to the target nerve as
described below:

Adductor canal.

Proximal: Inserted as described previously:

"…we performed an ultrasound survey at the medial part of the thigh, halfway between the
superior anterior iliac spine and the [superior border of the] patella. In a short axis view,
we identified the femoral artery underneath the sartorius muscle, with the vein just inferior
and the saphenous nerve just lateral to the artery."

Distal: Inserted as described previously:

"The transducer was initially placed on the medial aspect of the distal third of the thigh to
identify the femoral artery immediately deep to the sartorius muscle. The transducer was then
moved caudally along the long axis of the thigh until the femoral artery was seen diving deep
and moving away from the anterior muscle plane (sartorius and vastus medialis muscles),
toward the posterior aspect of the thigh where it becomes the popliteal artery. This area was
identified as the adductor hiatus, and the block location was selected 2 to 3 cm proximally
to this area, in the distal adductor canal."

Saline (10 mL) will be administered via the needle to dilate the space where the catheter is
to be inserted. A flexible non-stimulating perineural catheter (FlexTip, Arrow International,
Reading, PA, USA) will be inserted 3-5 cm past the needle tip; and the needle withdrawn over
the catheter. A 30 mL bolus of lidocaine 2% with 1:400,000 of epinephrine will then be
administered though the catheter. A "successful" catheter insertion will be defined as
decreased sensation to cold within the distribution of the saphenous nerve.

Popliteal-sciatic. Using an ultrasound, the bifurcation of the sciatic nerve will be
identified in short axis and marked at a point immediately distal at which point the two main
branches of the sciatic nerve are separate and a hypoechoic area can be viewed between the
two. This level will be marked on the skin.

Proximal: The needle will be inserted to intersect the sciatic nerve 6-7 cm proximal to the
mark on the skin (therefore, proximal to the sciatic bifurcation) and injection with saline
used to ensure subepimyseal spread.

Distal: The needle tip will be inserted into the hypoechoic area between the two branches of
the sciatic nerve immediately distal to the sciatic nerve bifurcation between the paraneurium
and epineurium (the subparaneural space/compartment). As described previously: "An adequate
position was defined as the presence of circular expansion of the paraneural sheath... Once
circular expansion was obtained, we injected. During the injection process, the Tuohy needle
was kept stationary and care was taken to ensure that neural swelling did not occur. The
latter was defined as an increase in the cross-sectional surface of the nerve. If neural
swelling was detected by US, the needle was carefully withdrawn before resuming the
injection."

A 40 mL bolus of normal saline or lidocaine 2% with 1:400,000 of epinephrine will then be
given though the needle. A flexible non-stimulating perineural catheter (FlexTip, Arrow
International, Reading, PA, USA) will be inserted 3-5 cm past the needle tip; and the needle
withdrawn over the catheter. If saline was administered pre-operatively, then the 40 mL of
lidocaine 2% with 1:400,000 of epinephrine will be administered through the catheter
following surgery. A "successful" catheter insertion will be defined as decrease in cutaneous
sensation to cold on the plantar aspect of the foot.

Intraop: Patients may receive a general and/or neuraxial anesthetic that would be determined
by the intraoperative anesthesia provider. Additional boluses of 10 mL 2% lidocaine with
epinephrine may be given, if needed, via the perineural catheter.

Perineural infusion: An infusion pump will be attached to each subject's perineural catheter.
The pump will provide ropivacaine 0.2% at 8 mL/h (adductor) or 6 mL/h (popliteal) basal rate
infusion and a 4 mL patient-controlled bolus with a 30 minute lockout (all standard at UCSD).

Data collection: All data collection will be through standard UCSD nursing/therapy EPIC notes
(adductor canal) or postoperative phone calls (popliteal) for the day following surgery.

Primary endpoint: The primary endpoint will be the average pain on post operative day 1
following surgery as measured on a numeric rating scale (0-10, 0=no pain, 10=worst imaginable
pain) during the time periods of 08:00-24:00 (adductor) or the two hours preceding the
data-collection phone call (popliteal).

Secondary endpoints: Popliteal subjects will be called the day following surgery to collect
information regarding surgical pain (Numeric Rating Scale of 0 to 10, with "0" being no pain
and "10" being the worst pain ever experienced), analgesic use (oral, IV, and infusion
boluses), infusion side effects, and distance ambulated (adductor catheters only). Popliteal
subjects will be called one week (+/- 1 day) following surgery to inquire about possible
block-related complications.

Sample size estimates:

Adductor canal. The primary analysis will utilize the Wilcoxon Rank Sum test. The figure
below shows the estimated density of post-op day 1 pain scores following Proximal insertion
(mean = 4.12, SD = 1.74) based on published data.10 To simulate power, The Investigators used
the truncated Gaussian distribution with range 0 to 10; SD=1.74; Proximal group mean = 4.12;
and Distal group means = 5, 5.5, 6, 6.5, 7, 6.5, and 8.

Under these assumptions and two-sided a = 5%, The Investigators simulated 10,000 trials with
sample size of 25 per group with a primary end point measurement.

The Investigators found the simulated power to be as plotted below [clinicaltrials.gov does
not support figures at this location].

So The Investigators have 80% power to detect group differences in pain as small as about
1.52.

Popliteal-sciatic. Using an expected NRS mean=2.6 and SD=2.1 of average pain on postoperative
day 1 (based on unpublished data from IRB study #101282), approximately 31 subjects in each
treatment arm with a primary end point measurement will be required to detect a difference
between treatment group means of 1.5. This is with a 2-sided alpha=0.05, beta=0.2, and
power=0.8 (ClinCalc.com accessed June 28, 2015). The Investigators will employ a t-test for
parametric data and Wilcoxon Rank Sum test for non-parametric data.

With the two locations combined, The Investigators will need 112 subjects with a primary end
point measurement; and, The Investigators will enroll up to 150 subjects to account for
drop-outs and subjects without a primary end point measurement.

** Of great importance: the popliteal-sciatic and adductor canal data will be analyzed and
reported completely separately--they will NOT be combined at any time.

Inclusion Criteria:

1. undergoing surgery with an adductor canal or popliteal-sciatic perineural catheter for
postoperative analgesia following primary tri-compartment knee arthroplasty or
foot/ankle surgery;

2. anticipated to have at least moderate pain following surgery [NRS>3]; and,

3. age 18 years or older.

Exclusion Criteria:

1. pregnancy (a urine pregnancy test is standard at UCSD for female patients prior to
menopause who are sexually active with the opposite sex within the previous year);

2. inability to communicate with the investigators and hospital staff;

3. clinical neuropathy in the surgical extremity;

4. chronic high-dose opioid use (defined as daily use for more than 4 weeks prior to
surgery of at least the equivalent of 20 mg oxycodone);

5. BMI > 40 kg/m2;

6. allergy to study medications (lidocaine, ropivicaine);

7. known renal insufficiency; or,

8. incarceration.