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

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ClinicalTrials.gov Identifier: NCT02439281
Recruitment Status : Completed
First Posted : May 8, 2015
Last Update Posted : August 17, 2018
Sponsor:
Information provided by (Responsible Party):
Mihaela Visoiu, University of Pittsburgh

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.


Condition or disease Intervention/treatment Phase
Postoperative Pain Drug: Clonidine Drug: Ropivacaine Not Applicable

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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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: ROPIVACAINE WITH CLONIDINE FOR PEDIATRIC RECTUS SHEATH BLOCKS- THE MAGIC COMBINATION? - A Double Blinded Prospective Study
Study Start Date : May 2015
Actual Primary Completion Date : May 1, 2018
Actual Study Completion Date : May 1, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Ropivacaine Group
Ropivacaine Group will receive ropivacaine 0.5% (10 ml) injected bilaterally in the posterior rectus sheath, at the umbilicus location.
Drug: Ropivacaine
One hundred pediatric patients (10-17 years old) scheduled for laparoscopic appendectomy will be randomized to the two treatment groups: the Ropivacaine Group will receive ropivacaine 0.5% (10 ml) injected bilateral in Both groups will receive ropivacaine 0.5% (10 ml) injected bilaterally for the rectus sheath block
Other Name: Naropin

Experimental: Ropivacaine/ Clonidine Group
Ropivacaine/ Clonidine Group will receive ropivacaine 0.5% (10 ml) and clonidine (2mcg/kg) injected bilaterally in the posterior rectus sheath, at the umbilicus location.
Drug: Clonidine
Only the Ropivacaine /clonidine group will receive clonidine (2mcg/kg) injected with ropivacaine.
Other Names:
  • kapvay
  • Catapres
  • Duraclon
  • Nexiclon

Drug: Ropivacaine
One hundred pediatric patients (10-17 years old) scheduled for laparoscopic appendectomy will be randomized to the two treatment groups: the Ropivacaine Group will receive ropivacaine 0.5% (10 ml) injected bilateral in Both groups will receive ropivacaine 0.5% (10 ml) injected bilaterally for the rectus sheath block
Other Name: Naropin




Primary Outcome Measures :
  1. Duration of sensory block (paresthesia) [ Time Frame: Indicated by return of normal sensation (expected average of 12 hours after block placement). ]
    The investigators hypothesize that rectus sheath injections with ropivacaine and clonidine result in longer duration of sensory block (paresthesia) compared to ropivacaine alone.


Secondary Outcome Measures :
  1. Satisfaction with pain control [ Time Frame: Prior to hospital discharge (up to 24 hours after surgery) ]
    The investigators hypothesize that rectus sheath injections with ropivacaine/ clonidine would result in better satisfaction with pain control.

  2. Complications rate [ Time Frame: up to 24 hours after surgery ]
    The investigators expect no difference in incidence of complications (e.g. oversedation, hypotension, bradycardia episodes, etc.).

  3. Change in anxiety scores [ Time Frame: Before surgery (baseline) and 6 hours after block placement ]
    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 Ropivacaine Group.

  4. Duration of analgesia at umbilicus instrument site [ Time Frame: indicated by the first request for pain medication (expected average of 12 hours post block placement) ]
    The investigators hypothesize that rectus sheath injections with ropivacaine/ clonidine would result in longer duration of analgesia and decreased pain scores compared to ropivacaine alone.

  5. Average pain severity at the umbilicus laparoscopic site [ Time Frame: 18 hours after surgery ]
    Scores will be obtained every 2 hours after PACU discharge up to 18 hours or until hospital discharge, whichever occurs first. The average of these scores will be evaluated.

  6. Medication Consumption [ Time Frame: 18 hours after surgery ]


Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02439281


Locations
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15201
Sponsors and Collaborators
Mihaela Visoiu
Investigators
Principal Investigator: Mihaela Visoiu, MD Children's Hospital of UPMC

Publications:
Spielberger Charles Donald ECD. State-trait Anxiety Inventory for Children: STAIC : How I Feel Questionnaire : Professional Manual 1973.

Responsible Party: Mihaela Visoiu, Director Acute Interventional Perioperative Pediatric Pain Service, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02439281     History of Changes
Other Study ID Numbers: PRO14100075
First Posted: May 8, 2015    Key Record Dates
Last Update Posted: August 17, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Mihaela Visoiu, University of Pittsburgh:
Ropivacaine
Anesthesia adjuncts
clonidine
laparoscopic appendectomy
rectus sheath block

Additional relevant MeSH terms:
Pain, Postoperative
Pain
Neurologic Manifestations
Nervous System Diseases
Postoperative Complications
Pathologic Processes
Signs and Symptoms
Ropivacaine
Clonidine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Analgesics
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action