Ropivacaine With Clonidine For Pediatric Rectus Sheath Blocks- The Magic Combination

Objective: The primary aim is to determine if ropivacaine combined with clonidine prolongs
duration of paresthesia at the umbilicus. The secondary aims are to determine if the use of
clonidine decreases anxiety level, prolongs duration of analgesia, decreases pain severity at
the umbilicus laparoscopic site, reduces the need for pain medication, improves satisfaction
with pain control, and is associated with complications such as oversedation, hypotension,
and bradycardia.

Specific Aims: Aim 1 will determine if the duration of sensory block (paresthesia) after
ultrasound guided single injections rectus sheath blocks performed with ropivacaine/
clonidine is longer than duration of paresthesia after rectus sheath blocks performed with
ropivacaine alone. The investigators hypothesize that rectus sheath injections with
ropivacaine and clonidine result in longer duration of sensory block (paresthesia) compared
to ropivacaine alone.

Aim 2 will determine if the use of clonidine decreases postoperative anxiety scores and if
postoperative pain scores correlate with anxiety scores. The investigators hypothesize that
patient postoperative anxiety scores are lower in the Ropivacaine/Clonidine group and
postoperative anxiety scores decrease more in Ropivacaine /Clonidine Group, than in the
Ropivacaine Group. The investigators expect that preoperative and postoperative Numeric
Rating Scale(NRS) scores reported by the patient will correlate moderately (0.3-0.49) to high
(equal /or >0.5) with preoperative and postoperative anxiety level.

Aim 3 will determine if rectus sheath injections with ropivacaine/ clonidine prolongs
duration of analgesia at umbilicus instrument site, decreases analgesic consumption, improves
satisfaction with pain control, and has minimal complications such as oversedation,
bradycardia, and hypotension. The investigators hypothesize that rectus sheath injections
with ropivacaine/ clonidine would result in longer duration of analgesia compared to
ropivacaine alone, lower pain scores at umbilicus, less need for pain medication consumption
for pain at umbilicus and for the first 18 hours, better satisfaction with pain control from
patient, parent and nurse. The investigators expect no difference in incidence of
oversedation, hypotension, and bradycardia episodes.

Background: Millions of pediatric patients undergo laparoscopic surgeries every year and many
of them suffer significant pain on the day of surgery and the subsequent days. Pain is a
sensory and emotional experience, modified by multiple factors, including anxiety. Patient's
anxiety correlates with the severity of pain. Children that are very anxious before surgery
have been found to have more postoperative pain, delayed hospital discharge, higher incidence
of emergence delirium, sleep disturbances, and other maladaptive behavior changes that can
last up to a few weeks following surgery. Laparoscopic appendectomy can cause significant
pain and anxiety despite the minimally invasive approach. The investigators' recent completed
prospective study showed that on the day after surgery, pain after laparoscopic appendectomy
correlated very well with postoperative anxiety scores (Pearson coefficient =0.539; pending
publication results from 133 subjects, 11-17 years old, that underwent laparoscopic
appendectomy).

Effective postoperative analgesia after laparoscopic appendectomy is necessary for optimal
recovery. A multimodal approach includes regional analgesia techniques, improves analgesia,
and reduces side-effects from opioids use. Unfortunately, pain associated with this procedure
extends after the day of surgery. Continuous peripheral nerve blocks can be effective, but
are deemed excessively invasive in the context of this minimally invasive surgery. Single
injection nerve blocks are appropriate, but the duration with a long acting local anesthetic
is only around 12 hours, and do not match the most painful part of postoperative period, the
first 24 hours. Over the last years, the challenge of developing a blocking agent that lasts
long enough to outlast pain and has minimal side effects has been addressed by combining
different drugs (epinephrine, clonidine, dexamethasone, tramadol, buprenorphine, midazolam,
magnesium, dexmedetomidine, and ketamine) and yielded mixed results. Among these, clonidine,
an alpha 2 adrenoreceptor agonist has been shown to prolong the duration of analgesia when
administered in epidural space in children. Clonidine has also been added to local anesthetic
for peripheral nerve blocks but its perineural use is controversial and the exact mechanism
is unclear. Its action is not entirely attributed to an alpha -adrenergic effect at the
nerve; rather, it is possibly secondary to the blockade of the current through
hyperpolarization- activated cyclic nucleotide-gated channels, resulting in the enhancement
of activity-dependent hyperpolarization.

From the limited available data, perineurally administered clonidine appears to be safe, but
the results remain controversial. Adult metaanalysis have found that clonidine from 30-300
mcg prolongs the time to the first analgesic request by only 2-2.5 hrs. Furthermore,
clonidine prolonged sensory and motor blockade with all local anesthetic except mepivacaine.

The pediatric literature regarding the use of clonidine for peripheral nerve blocks lags
behind adult literature and is conflicting. Few small and under-powered studies showed at
best a weak trend in favor of clonidine. A retrospective review of 215 patients showed that
the use of clonidine prolongs the duration of infraclavicular, lumbar plexus, femoral, fascia
iliaca and sciatic nerve blocks by 20-50%. However, the prolongation is block location
dependent, and increased the incidence of motor block. This effect was only seen with diluted
concentrations of bupivacaine 0.125% and ropivacaine 0.2%. No pediatric or adult studies were
performed involving trunk blocks such as rectus sheath, transversus abdominis plane, or
paravertebral nerve blocks.

Side effects reported after clonidine was administered neuraxially or perineurally are
hypotension, sedation, fainting, and prolonged motor blockade. Hypotension and sedation
appear to be limited up to doses of 150 mcg. However, Petroheilou et al. reported
intraoperatively hemodynamic stability after administration of clonidine at 3 mcg/kg.
Clonidine 1-2 mcg/kg is suggested for use with local anesthetic for single injections
peripheral nerve blocks.

Clonidine can help to relieve postoperative anxiety, and subsequently improve pain control.
Minimal sedation after clonidine administration can be desired for some pediatric patients.
Clonidine at 2 mcg/kg prevents sevoflurane-induced agitation and can be used as premedication
in children. No studies have investigated its role as an anxiolytic when added to local
anesthetic for a nerve block.

The Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (CHP of
UPMC) has a dedicated service to provide regional anesthesia techniques and performs
peripheral nerve blocks on a regular basis. Over the last academic year, 190 patients that
underwent laparoscopic appendectomy had peripheral nerve blocks (rectus sheath and
transversus abdominis plane) performed for pain control. Children localized the majority of
their pain to the umbilicus instrument site. This pain interferes with patients' activities
such as ambulation, eating, and bedside activities. The principal investigator performed a
retrospective chart review to compare postoperative analgesia from rectus sheath blocks and a
combination of transversus abdominis plane and rectus sheath blocks. The postoperative opioid
consumption and pain scores were similar. Since then, the primary investigator performs only
ultrasound guided rectus sheath blocks for postoperative analgesia after laparoscopic
appendectomy. A recent pediatric study showed that the rectus sheath blocks in combination
with multimodal analgesia are effective for postoperative pain control after mentioned
procedure. Unfortunately the duration of these blocks performed with maximum 20 ml of
bupivacaine 0.25% with adrenaline did not outlast the most painful period. The investigators
believe that rectus sheath blocks with ropivacaine 0.5% and clonidine (2 mcg/kg) will prolong
the duration of blocks, can reduce postoperative pain and anxiety, facilitate discharge, and
decrease unplanned hospital admission secondary to pain, and can contribute to an increased
patient and family satisfaction, and decrease costs for the hospital, insurer, and the
patient.

Significance: To the investigators' knowledge, this is the first study to investigate whether
ropivacaine /clonidine rectus sheath blockade is a better and more complete therapeutic
regimen for patients undergoing laparoscopic appendectomy. While the patients that underwent
uncomplicated laparoscopic appendectomy are treated as inpatient for at least one day, CHP
wants to implement early discharge strategies. Unfortunately, the pain after day of surgery
can be significant and some parents can be reluctant to have their children discharged. The
analgesia advices can be poorly retained. The parents can feel overwhelmed about home pain
management. Some parents believe that using pain medication in childhood may lead to later
drug abuse. This is concerning as parents often undermedicate their child's pain, with up to
60% of parents administering less than the prescribed analgesia on the following day after
surgery discharge. A child with long lasting pain control and less anxiety from
ropivacaine/clonidine rectus sheath blockade will help the parent cope with the surgical
event, and can facilitate early discharge.

Additionally, patient's satisfaction with pain control is becoming an increasingly important
aspect of health care reimbursements reported via the Hospital Assessment of Healthcare
Providers and Systems (HCAHPS) survey. The ropivacaine/ clonidine rectus sheath blockade in
combination with multimodal therapy can be better therapeutic regimen that standard of care,
and can improve quality of care, increase satisfaction and save health care costs.

Inclusion Criteria:

- age 10-17 years

- scheduled for elective laparoscopic appendectomy

- weight >/=34kg

- complete postoperative questionnaires.

Exclusion Criteria:

- patients younger than 10 years and 18 years or older

- weight < 34 kg

- weight >/=100 kg

- patient and family refusal

- non-English-speaking patients and families

- cognitive impairment

- developmental delay

- allergies to medications used in the study (hydromorphone, oxycodone, acetaminophen,
ketorolac, ropivacaine, and clonidine)

- need for opioids via patient controlled analgesia device

- patients with a positive pregnancy test

- local infection at planned injection sites

- patients with failed rectus sheath blocks

- patients that require opioids via patient controlled analgesia device

- patients with laparoscopic procedure converted to open

- patients that will not be able to place the time of return to normal sensation within
1 hour of its occurrence

- patients with no follow up possible

- the patients that will be discharged home before the resolution on paresthesia will be
excluded from analysis of the first aim.