Clinical trial NCT02439281: Ropivacaine With Clonidine For Pediatric Rectus Sheath Blocks- The Magic Combination
Official title: ROPIVACAINE WITH CLONIDINE FOR PEDIATRIC RECTUS SHEATH BLOCKS- THE MAGIC COMBINATION? - A Double Blinded Prospective Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Postoperative Pain
Keywords: Ropivacaine
Anesthesia adjuncts
clonidine
laparoscopic appendectomy
rectus sheath block
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2015-05-08
Enrollment: 50
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Duration of Sensory Block (Paresthesia)
timeFrame: Indicated by return of normal sensation (expected average of 12 hours after block placement).
Secondary outcomes:
measure: Satisfaction With Pain Control From Patient
timeFrame: Prior to hospital discharge (up to 24 hours after surgery)
measure: Complications Rate
timeFrame: until study completion
measure: Change in Anxiety Scores
timeFrame: 6 hours after block placement
measure: Duration of Analgesia at Umbilicus Instrument Site-How Many Minutes Passed From the Time When the Blocks Where Performed Until Patient Reported Pain at Umbilicus
timeFrame: indicated by the first request for pain medication at umbilicus site
measure: Average Pain Severity at the Umbilicus Laparoscopic Site
timeFrame: Logistic regression of the 4 th pain score assessment
measure: Medication Consumption
timeFrame: 18 hours after surgery
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of UPMC
name: Mihaela Visoiu, MD
role: PRINCIPAL_INVESTIGATOR
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