Ropivacaine With Clonidine For Pediatric Rectus Sheath Blocks- The Magic Combination
Ropivacaine With Clonidine For Pediatric Rectus Sheath Blocks- The Magic Combination
Background: Millions of pediatric patients undergo laparoscopic surgeries every year and many
 of them suffer significant pain and anxiety. Patient's anxiety correlates with the severity
 of pain and effective postoperative analgesia is necessary for optimal recovery. Single
 injections ultrasound guided rectus sheath blocks provide satisfactory postoperative
 analgesia after pediatric laparoscopic appendectomy, however they are short lived. Searching
 for a blocking agent that last long enough to outlast pain and has minimal side effects is a
 difficult task. Using a combination of drugs yielded mixed results. Few pediatric studies
 showed at best a weak trend in favor of clonidine prolonging analgesia after some blocks, but
 anxiolytic properties of clonidine were not investigated. This study will compare rectus
 sheath ropivacaine blocks with ropivacaine and clonidine blocks.

 Methods: One hundred pediatric patients (10-17 years old) scheduled for laparoscopic
 appendectomy will be double blinded and randomized to the two treatment groups: the
 Ropivacaine Group will receive ropivacaine 0.5% (10 ml) injected bilaterally in the posterior
 rectus sheath, at the umbilicus location, and Ropivacaine Clonidine Group will receive
 ropivacaine 0.5% (10 ml) and clonidine (2mcg/kg). Post-operative analgesia will be provided
 with ketorolac and acetaminophen around the clock, and morphine, or/and oxycodone as needed.
 The primary aim is to determine if ropivacaine combined with clonidine prolongs duration of
 paresthesia. The secondary aims are to determine if the use of clonidine decreases anxiety
 level, prolongs duration of analgesia, and decreases pain severity at umbilicus laparoscopic
 site, reduces the need for analgesics, improves satisfaction with pain control, and is
 associated with complications such as oversedation, hypotension, and bradycardia.

 Conclusions: Every hour of excellent analgesia count and a prolongation of block duration by
 at least 50% is clinical relevant. The investigators hypothesize that rectus sheath
 injections with ropivacaine and clonidine offer improved pain management compared to
 ropivacaine alone.
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.